Synthesis and biological evaluation of bis-N2, N2′-(4-hydroxycoumarin-3-yl) ethylidene]-2, 3-dihydroxysuccinodihydrazides
- Manyeruke, Meloddy H, Tshiwawa, Tendamudzimu, Hoppe, Heinrich C, Isaacs, Michelle, Seldon, Ronnett, Warner, Digby F, Krause, Rui W M, Kaye, Perry T
- Authors: Manyeruke, Meloddy H , Tshiwawa, Tendamudzimu , Hoppe, Heinrich C , Isaacs, Michelle , Seldon, Ronnett , Warner, Digby F , Krause, Rui W M , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193430 , vital:45331 , xlink:href="https://doi.org/10.1016/j.bmcl.2019.126911"
- Description: A series of N2,N2′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.
- Full Text:
- Date Issued: 2020
- Authors: Manyeruke, Meloddy H , Tshiwawa, Tendamudzimu , Hoppe, Heinrich C , Isaacs, Michelle , Seldon, Ronnett , Warner, Digby F , Krause, Rui W M , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193430 , vital:45331 , xlink:href="https://doi.org/10.1016/j.bmcl.2019.126911"
- Description: A series of N2,N2′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.
- Full Text:
- Date Issued: 2020
Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands
- Adeyemi, Christiana M, Hoppe, Heinrich C, Isaacs, Michelle, Mnkandhla, Dumisani, Lobb, Kevin A, Klein, Rosalyn, Kaye, Perry T
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Mnkandhla, Dumisani , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451171 , vital:75025 , xlink:href="https://doi.org/10.1016/j.bioorg.2020.104280"
- Description: A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-D-xylulose-5- phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+- chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6–16.4 µM against Plasmodium falciparum parasites and IC50 values of 5.2 – 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Mnkandhla, Dumisani , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451171 , vital:75025 , xlink:href="https://doi.org/10.1016/j.bioorg.2020.104280"
- Description: A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-D-xylulose-5- phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+- chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6–16.4 µM against Plasmodium falciparum parasites and IC50 values of 5.2 – 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
Biological activity of plant extracts and isolated compounds from Alchornea laxiflora: Anti-HIV, antibacterial and cytotoxicity evaluation
- Ndinteh, Derek T, Olivier, Denise K, Noundou, Xavier S, Krause, Rui W M, Mnkandhla, D, Isaacs, Michelle, Hoppe, Heinrich C, Muganza, F M, Mbafor, J T, Van Vuuren, S F, Patnala, S
- Authors: Ndinteh, Derek T , Olivier, Denise K , Noundou, Xavier S , Krause, Rui W M , Mnkandhla, D , Isaacs, Michelle , Hoppe, Heinrich C , Muganza, F M , Mbafor, J T , Van Vuuren, S F , Patnala, S
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126634 , vital:35907 , https://doi.org/10.1016/j.sajb.2018.08.010
- Description: This study was designed to assess the cytotoxicity, anti-HIV and antibacterial efficacy of various solvent extracts of roots, stem and leaves of Alchornea laxiflora, as well as five compounds isolated from its methanolic stem extract viz.; ellagic acid (1); 3-O-methyl-ellagic acid (2), 3-O-β-d-glucopyranosyl-β-sitosterol (3), 3-O-acetyl-oleanolic acid (4) and 3-O-acetyl-ursolic acid (5). The tested crude extracts were prepared from several solvent polarities including: hexane (Hex), chloroform (CHCl3), ethyl acetate (EtOAc), ethanol (EtOH), methanol (MeOH) and water (H2O). The anti-HIV properties were assessed on HIV-1 subtype C integrase while the cytotoxicity was tested against Hela cells. The antibacterial activity was studied on a panel of pathogens including gastrointestinal, skin, respiratory and urinary-tract infection causing Gram positive bacteria viz.; Bacillus cereus (ATCC 11778), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25923) and Staphylococcus saprophyticus (ATCC 15305)] and Gram-negative bacteria, i.e., Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Moraxella catarrhalis (ATCC 23246). All the tested samples were determined to be non-toxic due to the low inhibitions observed. The most potent anti-HIV activity was observed for the methanolic extract of A. laxiflora root (ALR4) with an IC50 value of 0.21 ng/ml, which was more active than chicoric acid used as reference drug (6.82 nM). Roots, stem and leaves of A. laxiflora extracts exhibited antibacterial activities against most of the Gram-positive bacteria with the minimum inhibitory concentrations (MIC) ranging between 50 and 63 μg/ml. Compounds 1–5 displayed antibacterial activities against S. saprophyticus with MIC values as low as 4 μg/ml. The results inferred from this study demonstrate the potential of A. laxiflora root as a source for new anti-HIV drugs and scientifically validate the traditional use of A. laxiflora in the treatment of gastrointestinal, skin, respiratory and urinary tract related infections. These results reaffirm the ethnopharmacological significance of African traditional medicines.
- Full Text:
- Date Issued: 2018
- Authors: Ndinteh, Derek T , Olivier, Denise K , Noundou, Xavier S , Krause, Rui W M , Mnkandhla, D , Isaacs, Michelle , Hoppe, Heinrich C , Muganza, F M , Mbafor, J T , Van Vuuren, S F , Patnala, S
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126634 , vital:35907 , https://doi.org/10.1016/j.sajb.2018.08.010
- Description: This study was designed to assess the cytotoxicity, anti-HIV and antibacterial efficacy of various solvent extracts of roots, stem and leaves of Alchornea laxiflora, as well as five compounds isolated from its methanolic stem extract viz.; ellagic acid (1); 3-O-methyl-ellagic acid (2), 3-O-β-d-glucopyranosyl-β-sitosterol (3), 3-O-acetyl-oleanolic acid (4) and 3-O-acetyl-ursolic acid (5). The tested crude extracts were prepared from several solvent polarities including: hexane (Hex), chloroform (CHCl3), ethyl acetate (EtOAc), ethanol (EtOH), methanol (MeOH) and water (H2O). The anti-HIV properties were assessed on HIV-1 subtype C integrase while the cytotoxicity was tested against Hela cells. The antibacterial activity was studied on a panel of pathogens including gastrointestinal, skin, respiratory and urinary-tract infection causing Gram positive bacteria viz.; Bacillus cereus (ATCC 11778), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25923) and Staphylococcus saprophyticus (ATCC 15305)] and Gram-negative bacteria, i.e., Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Moraxella catarrhalis (ATCC 23246). All the tested samples were determined to be non-toxic due to the low inhibitions observed. The most potent anti-HIV activity was observed for the methanolic extract of A. laxiflora root (ALR4) with an IC50 value of 0.21 ng/ml, which was more active than chicoric acid used as reference drug (6.82 nM). Roots, stem and leaves of A. laxiflora extracts exhibited antibacterial activities against most of the Gram-positive bacteria with the minimum inhibitory concentrations (MIC) ranging between 50 and 63 μg/ml. Compounds 1–5 displayed antibacterial activities against S. saprophyticus with MIC values as low as 4 μg/ml. The results inferred from this study demonstrate the potential of A. laxiflora root as a source for new anti-HIV drugs and scientifically validate the traditional use of A. laxiflora in the treatment of gastrointestinal, skin, respiratory and urinary tract related infections. These results reaffirm the ethnopharmacological significance of African traditional medicines.
- Full Text:
- Date Issued: 2018
Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.
- Mbaba, Mziyanda, de la Mare, Jo-Anne, Sterrenberg, Jason N, Kajewole, Deborah, Maharaj, Shantal, Edkins, Adrienne L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
- Full Text:
- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
- Full Text:
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers:
- Lunga, Mayibongwe J, Chisango, Ruramai L, Weyers, Carli, Isaacs, Michelle, Taylor, Dale, Edkins, Adrienne L, Khanye, Setshaba D, Hoppe, Heinrich C, Veale, Clinton G L
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
- Date Issued: 2018
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
- Date Issued: 2018
Ferrocenyl and organic novobiocin derivatives: synthesis and their in vitro biological activity
- Mbaba, Mziyanda, Mabhula, Amanda N, Boel, Natasha, Edkins, Adrienne L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , Mabhula, Amanda N , Boel, Natasha , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66189 , vital:28914 , https://doi.org/10.1016/j.jinorgbio.2017.04.014
- Description: publisher version , A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a–d/6f showing enhanced activity compared to organic analogues 5a–b and 5e–f.
- Full Text: false
- Date Issued: 2017
- Authors: Mbaba, Mziyanda , Mabhula, Amanda N , Boel, Natasha , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66189 , vital:28914 , https://doi.org/10.1016/j.jinorgbio.2017.04.014
- Description: publisher version , A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a–d/6f showing enhanced activity compared to organic analogues 5a–b and 5e–f.
- Full Text: false
- Date Issued: 2017
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers.
- Lunga, Mayibongwe J, Chisango, Ruramai Lissa, Weyers, Carli, Isaacs, Michelle, Taylor, Dale, Edkins, Adrienne L, Khanye, Setshaba D, Hoppe, Heinrich C, Veale, Clinton G L
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai Lissa , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122908 , vital:35370 , https://doi.org/10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐cyanophenyl)thio]ethanone (13) and 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non‐haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long‐term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
- Full Text:
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai Lissa , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122908 , vital:35370 , https://doi.org/10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐cyanophenyl)thio]ethanone (13) and 1‐(5‐chloro‐1H‐indol‐3‐yl)‐2‐[(4‐nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non‐haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long‐term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
- Full Text:
NMR structural elucidation of channaine, an unusual alkaloid from Sceletium tortuosum:
- Veale, Clinton G L, Chen, Weiyang, Chaudhary, Sushil, Kituyi, Sarah N, Isaacs, Michelle, Hoppe, Heinrich C, Edkins, Adrienne L, Combrinck, Sandra, Mehari, Bewketu, Viljoen, Alvaro
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
- Authors: Veale, Clinton G L , Chen, Weiyang , Chaudhary, Sushil , Kituyi, Sarah N , Isaacs, Michelle , Hoppe, Heinrich C , Edkins, Adrienne L , Combrinck, Sandra , Mehari, Bewketu , Viljoen, Alvaro
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164345 , vital:41110 , DOI: 10.1016/j.phytol.2017.11.018
- Description: Chemical interrogation of the Sceletium genus and Amaryllidaceae family of plants has yielded a diverse array of aryl-hydroindole containing alkaloids. Included in this class is channaine, which was tentatively identified, without comprehensive structural elucidation from Sceletium tortuosum in 1957. Following its isolation from S. strictum, the structure of channaine was eventually resolved by X-ray crystallographic analysis, which revealed an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits. However, since this report in 1978, channaine has not re-appeared in the literature. In this letter, the full NMR characterisation of channaine, isolated from S. tortuosum collected from St Helena in the Western Cape Province of South Africa, is reported for the first time.
- Full Text:
- Date Issued: 2018
Synthesis and evaluation of substituted 4-(N-benzylamino)cinnamate esters as potential anti-cancer agents and HIV-1 integrase inhibitors
- Faridoon, H, Edkins, Adrienne L, Isaacs, Michelle, Mnkandhla, Dumisani, Hoppe, Heinrich C, Kaye, Perry T
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
- Authors: Faridoon, H , Edkins, Adrienne L , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66289 , vital:28929 , https://doi.org/10.1016/j.bmcl.2016.05.023
- Description: publisher version , Encouraging selectivity and low micromolar activity against HeLa cervical carcinoma (IC50 ⩾ 3.0 μM) and the aggressive MDA-MB-231 triple negative breast carcinoma (IC50 ⩾ 9.6 μM) cell lines has been exhibited by a number of readily accessible 4-(N-benzylamino)cinnamate esters. The potential of the ligands as HIV-1 integrase inhibitors has also been examined.
- Full Text: false
- Date Issued: 2016
Preparation and characterization of isoniazid-loaded crude soybean lecithin liposomes
- Nkanga, Christian I, Isaacs, Michelle, Noundou, Xavier S, Krause, Rui W M, Walker, Roderick B
- Authors: Nkanga, Christian I , Isaacs, Michelle , Noundou, Xavier S , Krause, Rui W M , Walker, Roderick B
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125654 , vital:35804 , https://doi.org/10.1016/j.ijpharm.2017.04.074
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
- Authors: Nkanga, Christian I , Isaacs, Michelle , Noundou, Xavier S , Krause, Rui W M , Walker, Roderick B
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125654 , vital:35804 , https://doi.org/10.1016/j.ijpharm.2017.04.074
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
Synthesis, structure and in vitro anti-trypanosomal activity of non-toxic Arylpyrrole-Based Chalcone derivatives:
- Zulu, Ayanda I, Oderinlo, Ogunyemi O, Kruger, Cuan, Isaacs, Michelle, Hoppe, Heinrich C, Smith, Vincent J, Veale, Clinton G L, Khanye, Setshaba D
- Authors: Zulu, Ayanda I , Oderinlo, Ogunyemi O , Kruger, Cuan , Isaacs, Michelle , Hoppe, Heinrich C , Smith, Vincent J , Veale, Clinton G L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/179017 , vital:40096 , https://doi.org/10.3390/molecules25071668
- Description: With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.
- Full Text:
- Date Issued: 2020
- Authors: Zulu, Ayanda I , Oderinlo, Ogunyemi O , Kruger, Cuan , Isaacs, Michelle , Hoppe, Heinrich C , Smith, Vincent J , Veale, Clinton G L , Khanye, Setshaba D
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/179017 , vital:40096 , https://doi.org/10.3390/molecules25071668
- Description: With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.
- Full Text:
- Date Issued: 2020
New thiazolidine-2,4-dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity
- Oderinlo, Ogunyemi O, Tukulula, Matshawandile, Isaacs, Michelle, Taylor, Dale, Smith, Vincent J, Khanye, Setshaba D, Hoppe, Heinrich C
- Authors: Oderinlo, Ogunyemi O , Tukulula, Matshawandile , Isaacs, Michelle , Taylor, Dale , Smith, Vincent J , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122978 , vital:35382 , https://doi.org/10.1002/aoc.4385
- Description: Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.
- Full Text:
- Date Issued: 2018
- Authors: Oderinlo, Ogunyemi O , Tukulula, Matshawandile , Isaacs, Michelle , Taylor, Dale , Smith, Vincent J , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122978 , vital:35382 , https://doi.org/10.1002/aoc.4385
- Description: Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.
- Full Text:
- Date Issued: 2018
Anti-cancer and anti-trypanosomal properties of alkaloids from the root bark of Zanthoxylum leprieurii Guill and Perr
- Eze, Fabian I, Siwe-Noundou, Xavier, Isaacs, Michelle, Patala, Srivinas, Osadebe, Patience O, Krause, Rui W M
- Authors: Eze, Fabian I , Siwe-Noundou, Xavier , Isaacs, Michelle , Patala, Srivinas , Osadebe, Patience O , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193352 , vital:45324 , xlink:href="http://dx.doi.org/10.4314/tjpr.v19i11.19"
- Description: Purpose: To isolate the anti-cancer and anti-trypanosomal principles of Zanthoxylum leprieurii, a medicinally versatile wild tropical plant used for managing tumours, African trypanosomiasis, and inflammation in southeastern Nigeria. Methods: The pure compounds were isolated using chromatographic methods. The structural elucidation of the pure compounds was based on their NMR (1D and 2D) and mass spectral data as well as chemical test results. Structure-activity relationships were based on the structural differences among the compounds. The cytotoxicity of the extracts and compounds (1, 2, 3, and 4) was evaluated in HeLa (human cervix adenocarcinoma) cell line while the trypanocidal activities were evaluated on Trypanosoma brucei brucei. Results: Two acridone alkaloids, 1-hydroxy-3-methoxy-10-methylacridin-9 (10H)-one, named fabiocinine (1), and 1-hydroxy-2,3-dimethoxy-10-methylacridin-9 (10H)-one (arborinine, 2), together with a furoquinoline alkaloid, skimmianine (3), and a chelerythrine derivative, 6-acetonyl-5,6-dihydrochelerythrine (4) were isolated from the root bark of Zanthoxylum leprieurii. Skimmianine (3) exhibited cytotoxicity and anti-trypanosomal IC50 of 12.8 and 13.2 µg/mL respectively (p less than 0.05). Compound (1) and arborinine (2) were selectively cytotoxic to HeLa cells with cytotoxicity IC50 of 28.49 and 62.71 µg/mL, respectively, while (4) did not show significant activity (p less than 0.05). Conclusion: Zanthoxylum leprieurii root bark contains cytotoxic and trypanocidal compounds, and is thus a potential source of anti-cancer and anti-trypanosomal leads.
- Full Text:
- Date Issued: 2020
- Authors: Eze, Fabian I , Siwe-Noundou, Xavier , Isaacs, Michelle , Patala, Srivinas , Osadebe, Patience O , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193352 , vital:45324 , xlink:href="http://dx.doi.org/10.4314/tjpr.v19i11.19"
- Description: Purpose: To isolate the anti-cancer and anti-trypanosomal principles of Zanthoxylum leprieurii, a medicinally versatile wild tropical plant used for managing tumours, African trypanosomiasis, and inflammation in southeastern Nigeria. Methods: The pure compounds were isolated using chromatographic methods. The structural elucidation of the pure compounds was based on their NMR (1D and 2D) and mass spectral data as well as chemical test results. Structure-activity relationships were based on the structural differences among the compounds. The cytotoxicity of the extracts and compounds (1, 2, 3, and 4) was evaluated in HeLa (human cervix adenocarcinoma) cell line while the trypanocidal activities were evaluated on Trypanosoma brucei brucei. Results: Two acridone alkaloids, 1-hydroxy-3-methoxy-10-methylacridin-9 (10H)-one, named fabiocinine (1), and 1-hydroxy-2,3-dimethoxy-10-methylacridin-9 (10H)-one (arborinine, 2), together with a furoquinoline alkaloid, skimmianine (3), and a chelerythrine derivative, 6-acetonyl-5,6-dihydrochelerythrine (4) were isolated from the root bark of Zanthoxylum leprieurii. Skimmianine (3) exhibited cytotoxicity and anti-trypanosomal IC50 of 12.8 and 13.2 µg/mL respectively (p less than 0.05). Compound (1) and arborinine (2) were selectively cytotoxic to HeLa cells with cytotoxicity IC50 of 28.49 and 62.71 µg/mL, respectively, while (4) did not show significant activity (p less than 0.05). Conclusion: Zanthoxylum leprieurii root bark contains cytotoxic and trypanocidal compounds, and is thus a potential source of anti-cancer and anti-trypanosomal leads.
- Full Text:
- Date Issued: 2020
In vitro Anti-trypanosomal activities of indanone-based chalcones:
- Beteck, Richard M, Legoabe, Lesetje J, Isaacs, Michelle, Hoppe, Heinrich C
- Authors: Beteck, Richard M , Legoabe, Lesetje J , Isaacs, Michelle , Hoppe, Heinrich C
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158280 , vital:40169 , https://doi.org/10.3354/meps12953
- Description: Human African trypanosomiasis is a neglected infectious disease that affects mostly people living in the rural areas of Africa. Current treatment options are limited to just four drugs that have been in use of four to nine decades. The life-threatening toxic side-effects associated with the use of these drugs are disconcerting. Poor efficacy, low oral bioavailability, and high cost are other shortcomings of current HAT treatments. Evaluating the potentials of known hits for other therapeutic areas may be a fast and convenient method to discover new hit compounds against alternative targets. A library of 34 known indanone based chalcones was screened against T.b. brucei and nine potent hits, having IC50 values between 0.5–8.9 µM, were found. The SAR studies of this series could provide useful information in guiding future exploration of this class of compounds in search of more potent, safe, and low cost anti-trypanosomal agents.
- Full Text:
- Date Issued: 2019
- Authors: Beteck, Richard M , Legoabe, Lesetje J , Isaacs, Michelle , Hoppe, Heinrich C
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/158280 , vital:40169 , https://doi.org/10.3354/meps12953
- Description: Human African trypanosomiasis is a neglected infectious disease that affects mostly people living in the rural areas of Africa. Current treatment options are limited to just four drugs that have been in use of four to nine decades. The life-threatening toxic side-effects associated with the use of these drugs are disconcerting. Poor efficacy, low oral bioavailability, and high cost are other shortcomings of current HAT treatments. Evaluating the potentials of known hits for other therapeutic areas may be a fast and convenient method to discover new hit compounds against alternative targets. A library of 34 known indanone based chalcones was screened against T.b. brucei and nine potent hits, having IC50 values between 0.5–8.9 µM, were found. The SAR studies of this series could provide useful information in guiding future exploration of this class of compounds in search of more potent, safe, and low cost anti-trypanosomal agents.
- Full Text:
- Date Issued: 2019
Indolyl-3-ethanone-α-thioethers: a promising new class of non-toxic antimalarial agents
- Svogie, Archibald L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Veale, Clinton G L
- Authors: Svogie, Archibald L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Veale, Clinton G L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66233 , vital:28920 , https://doi.org/10.1016/j.ejmech.2016.02.056
- Description: publisher version , The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. Synthesis of a focused library of compounds revealed important insight into the SAR of this class of compounds, including critical information regarding the position and chemical nature of substituents on both the thiophenol and indole rings. This investigation ultimately led to the discovery of two hit compounds (16 and 27) which exhibited nano molar in vitro antimalarial activity coupled to no observable toxicity against a HeLa cell line.
- Full Text: false
- Date Issued: 2016
- Authors: Svogie, Archibald L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Veale, Clinton G L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66233 , vital:28920 , https://doi.org/10.1016/j.ejmech.2016.02.056
- Description: publisher version , The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. Synthesis of a focused library of compounds revealed important insight into the SAR of this class of compounds, including critical information regarding the position and chemical nature of substituents on both the thiophenol and indole rings. This investigation ultimately led to the discovery of two hit compounds (16 and 27) which exhibited nano molar in vitro antimalarial activity coupled to no observable toxicity against a HeLa cell line.
- Full Text: false
- Date Issued: 2016
Synthesis and anti-parasitic activity of C-benzylated (N-arylcarbamoyl) alkylphosphonate esters
- Adeyemi, Christiana Modupe, Isaacs, Michelle, Mnkandhla, Dumisani, Krause, Rui W M, Klein, Rosalyn, Hoppe, Heinrich C, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.
- Gumbo, Maureen, Beteck, Richard M, Mandizvo, Tawanda, Seldon, Ronnett, Warner, Digby F, Hoppe, Heinrich C, Isaacs, Michelle, Laming, Dustin, Tam, Christina C, Cheng, Luisa W, Liu, Nicole, Land, Kirkwood, Khanye, Setshaba D
- Authors: Gumbo, Maureen , Beteck, Richard M , Mandizvo, Tawanda , Seldon, Ronnett , Warner, Digby F , Hoppe, Heinrich C , Isaacs, Michelle , Laming, Dustin , Tam, Christina C , Cheng, Luisa W , Liu, Nicole , Land, Kirkwood , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122879 , vital:35362 , https://doi.org/10.3390/molecules23082038
- Description: Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
- Full Text:
- Authors: Gumbo, Maureen , Beteck, Richard M , Mandizvo, Tawanda , Seldon, Ronnett , Warner, Digby F , Hoppe, Heinrich C , Isaacs, Michelle , Laming, Dustin , Tam, Christina C , Cheng, Luisa W , Liu, Nicole , Land, Kirkwood , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122879 , vital:35362 , https://doi.org/10.3390/molecules23082038
- Description: Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
- Full Text:
Application of the Morita-Baylis-Hillman reaction in the synthesis of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1 integrase inhibitors
- Sekgota, Khethobole C, Majumder, Swarup, Isaacs, Michelle, Mnkandhla, Dumisani, Hoppe, Heinrich C, Khanye, Setshaba D, Kriel, Frederik H, Coates, Judy, Kaye, Perry T
- Authors: Sekgota, Khethobole C , Majumder, Swarup , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Khanye, Setshaba D , Kriel, Frederik H , Coates, Judy , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66178 , vital:28913 , https://doi.org/10.1016/j.bioorg.2017.09.015
- Description: publisher version , A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.
- Full Text: false
- Date Issued: 2017
- Authors: Sekgota, Khethobole C , Majumder, Swarup , Isaacs, Michelle , Mnkandhla, Dumisani , Hoppe, Heinrich C , Khanye, Setshaba D , Kriel, Frederik H , Coates, Judy , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66178 , vital:28913 , https://doi.org/10.1016/j.bioorg.2017.09.015
- Description: publisher version , A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.
- Full Text: false
- Date Issued: 2017
Synthesis, in vitro cytotoxicity and trypanocidal evaluation of novel 1, 3, 6-substituted non-fluoroquinolones
- Beteck, Richard M, Isaacs, Michelle, Khanye, Setshaba D, Hoppe, Heinrich C
- Authors: Beteck, Richard M , Isaacs, Michelle , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123140 , vital:35409 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Sleeping sickness (trypanosomiasis) is a neglected tropical disease that affects mostly the poorest communities in sub-Saharan Africa. Toxic side effects associated with the use of current anti-trypanosomal drugs, which in some cases kill faster than the disease itself, necessitate the search for new drugs with better safety margins. To this effect, a small library bearing different substituents at position -1, -3, and -6 of the quinolone nucleus were synthesized and evaluated in vitro against HeLa cell lines and Trypanosoma brucei brucei for cytotoxicity and trypanocidal potentials, respectively. While most of these compounds showed no cytotoxic effect, they exhibited moderate to weak anti-trypanosomal activities. The SAR studies of this series provide new information worth considering in future exploration of the quinolone scaffold in search ofmore potent and safe trypanocidal agents.
- Full Text:
- Date Issued: 2018
- Authors: Beteck, Richard M , Isaacs, Michelle , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123140 , vital:35409 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Sleeping sickness (trypanosomiasis) is a neglected tropical disease that affects mostly the poorest communities in sub-Saharan Africa. Toxic side effects associated with the use of current anti-trypanosomal drugs, which in some cases kill faster than the disease itself, necessitate the search for new drugs with better safety margins. To this effect, a small library bearing different substituents at position -1, -3, and -6 of the quinolone nucleus were synthesized and evaluated in vitro against HeLa cell lines and Trypanosoma brucei brucei for cytotoxicity and trypanocidal potentials, respectively. While most of these compounds showed no cytotoxic effect, they exhibited moderate to weak anti-trypanosomal activities. The SAR studies of this series provide new information worth considering in future exploration of the quinolone scaffold in search ofmore potent and safe trypanocidal agents.
- Full Text:
- Date Issued: 2018
Synthesis, antiplasmodial and antitrypanosomal evaluation of a series of novel 2-oxoquinoline-based thiosemicarbazone derivatives
- Darrell, Oliver T, Hulushe, Siyabonga T, Mtshare, Thanduxolo Elihle, Beteck, Richard M, Isaacs, Michelle, Laming, Dustin, Khanye, Setshaba D, Hoppe, Heinrich C, Krause, Rui W M
- Authors: Darrell, Oliver T , Hulushe, Siyabonga T , Mtshare, Thanduxolo Elihle , Beteck, Richard M , Isaacs, Michelle , Laming, Dustin , Khanye, Setshaba D , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123117 , vital:35407 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Herein a series of novel thiosemicarbazones (TSCs) derived from 2-oxoquinoline scaffold is reported, and the target compounds have been successfully synthesized and characterized using standard spectroscopic techniques. The in vitro biological activities of synthesized molecules were evaluated against Plasmodium falciparum malaria parasites (strain 3D7), Trypanosoma brucei brucei parasites (strain 427) and HeLa cells. All the compounds displayed modest or no activity at a concentration of 20 μM and percentage viability of >50 % was often observed. Except for compound 9o, none of the final compounds exhibited cytotoxic effects against HeLa cells at 20 μM.
- Full Text:
- Date Issued: 2018
- Authors: Darrell, Oliver T , Hulushe, Siyabonga T , Mtshare, Thanduxolo Elihle , Beteck, Richard M , Isaacs, Michelle , Laming, Dustin , Khanye, Setshaba D , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123117 , vital:35407 , https://doi.org/10.17159/0379-4350/2018/v71a25
- Description: Herein a series of novel thiosemicarbazones (TSCs) derived from 2-oxoquinoline scaffold is reported, and the target compounds have been successfully synthesized and characterized using standard spectroscopic techniques. The in vitro biological activities of synthesized molecules were evaluated against Plasmodium falciparum malaria parasites (strain 3D7), Trypanosoma brucei brucei parasites (strain 427) and HeLa cells. All the compounds displayed modest or no activity at a concentration of 20 μM and percentage viability of >50 % was often observed. Except for compound 9o, none of the final compounds exhibited cytotoxic effects against HeLa cells at 20 μM.
- Full Text:
- Date Issued: 2018