Synthesis and conformational studies of 5-bromo-1-[(N-substituted-carbamoyl) methyl]-7-azabenzimidazoles
- Oluwafemi, Kola A, Klein, Rosalyn, Lobb, Kevin A, Tshiwawa, Tendamudzimu, Isaacs, Michelle, Hoppe, Heinrich C, Kaye, Perry T
- Authors: Oluwafemi, Kola A , Klein, Rosalyn , Lobb, Kevin A , Tshiwawa, Tendamudzimu , Isaacs, Michelle , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452800 , vital:75171 , xlink:href="https://doi.org/10.1016/j.molstruc.2022.133811"
- Description: The Cs2CO3-catalysed condensation of 5-bromo-7-azabenzimidazole with a series of bromomethyl ketones has afforded a small library of ten, novel 5-bromo-1-[(N-substututed-carbamoyl)methyl]-7-azabenzimidazoles. Rotamerism in the products, as evidenced by the splitting of 1H- and 13C-NMR signals, is attributed to hindered internal rotation about the amide N-C(=O) bond, and has been explored using dynamic NMR (DNMR) analysis and computational methods at the GIAO B3LYP/6-311+G(2d,p) level of theory. Coalescence temperatures have been obtained for representative examples and rotational barriers determined experimentally and theoretically. A detailed theoretical analysis has been undertaken to explore conformations which may contribute to the relative populations of the s-cis and s-trans rotamers. The products have also been screened for cytotoxicity and activity against two parasitic protozoan strains (Plasmodium falciparum and Trypanosoma brucei).
- Full Text:
- Date Issued: 2022
- Authors: Oluwafemi, Kola A , Klein, Rosalyn , Lobb, Kevin A , Tshiwawa, Tendamudzimu , Isaacs, Michelle , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452800 , vital:75171 , xlink:href="https://doi.org/10.1016/j.molstruc.2022.133811"
- Description: The Cs2CO3-catalysed condensation of 5-bromo-7-azabenzimidazole with a series of bromomethyl ketones has afforded a small library of ten, novel 5-bromo-1-[(N-substututed-carbamoyl)methyl]-7-azabenzimidazoles. Rotamerism in the products, as evidenced by the splitting of 1H- and 13C-NMR signals, is attributed to hindered internal rotation about the amide N-C(=O) bond, and has been explored using dynamic NMR (DNMR) analysis and computational methods at the GIAO B3LYP/6-311+G(2d,p) level of theory. Coalescence temperatures have been obtained for representative examples and rotational barriers determined experimentally and theoretically. A detailed theoretical analysis has been undertaken to explore conformations which may contribute to the relative populations of the s-cis and s-trans rotamers. The products have also been screened for cytotoxicity and activity against two parasitic protozoan strains (Plasmodium falciparum and Trypanosoma brucei).
- Full Text:
- Date Issued: 2022
In vitro antimalarial, antitrypanosomal and HIV-1 integrase inhibitory activities of two Cameroonian medicinal plants
- Fouokeng, Yannick, Feumo Feusso, H M, Mbosso Teinkela, Jean E, Siwe-Noundou, Xavier, Wintjens, René T, Isaacs, Michelle, Hoppe, Heinrich C, Krause, Rui W M, Azébazé, Anatole G B, Vardamides, Juliette C
- Authors: Fouokeng, Yannick , Feumo Feusso, H M , Mbosso Teinkela, Jean E , Siwe-Noundou, Xavier , Wintjens, René T , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Azébazé, Anatole G B , Vardamides, Juliette C
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195014 , vital:45519 , xlink:href="https://doi.org/10.1016/j.sajb.2018.10.008"
- Description: Antiplasmodial, antitrypanosomal and anti-HIV-1 activities of crude extracts, fractions and some isolated compounds from two Cameroonian medicinal plants: Antrocaryon klaineanum Pierre (Anacardiaceae) and Diospyros conocarpa Gürke ex K. Schum. (Ebenaceae) were assessed. The phytochemical studies led to the isolation of eight compounds (1–8) from Diospyros conocarpa and six compounds (6, 9–13) from Antrocaryon klaineanum. These compounds were identified as mangiferolic acid (1), 3β, 22(S)-dihydroxycycloart-24E-en-26-oic acid (2), lupeol (3), aridanin (4), betulin (5), betulinic acid (6), bergenin (7), D-quercitol(8), entilin C(9), entilin A(10), antrocarine A(11), 7R,20(S)-dihydroxy-4,24(28)-ergostadien-3-one(12) and stigmasterol glucoside (13). The criteria for activity were set as follows: an IC50 value more than 10 μg/mL for crude extracts and more than 1 μg/mL for pure compounds. The hexane/ethyl acetate (1:1) fraction of A.klaineanum root bark (AKERF1) and the hexane/ethyl acetate (1:1) fraction of A.klaineanum trunk bark (AKETF1) presented the strongest antiplasmodial activities with IC50 values of 0.4 and 4.4 μg/mL, respectively. Aridanin (4) and antrocarine A(11), as well as the crude extract of D.conocarpa roots (EDCR), AKERF1 and AKETF1 showed moderate trypanocidal effects. The crude extract of A.klaineanum root bark (AKER) and AKETF1 exhibited attractive activities on HIV-1 integrase with IC50 values of 1.96 and 24.04 μg/mL, respectively. The results provide baseline information on the use of A.klaineanum and D.conocarpa extracts, as well as certain components, as sources of new antiplasmodial, antitrypanosomal and anti-HIV drugs.
- Full Text:
- Date Issued: 2019
- Authors: Fouokeng, Yannick , Feumo Feusso, H M , Mbosso Teinkela, Jean E , Siwe-Noundou, Xavier , Wintjens, René T , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Azébazé, Anatole G B , Vardamides, Juliette C
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195014 , vital:45519 , xlink:href="https://doi.org/10.1016/j.sajb.2018.10.008"
- Description: Antiplasmodial, antitrypanosomal and anti-HIV-1 activities of crude extracts, fractions and some isolated compounds from two Cameroonian medicinal plants: Antrocaryon klaineanum Pierre (Anacardiaceae) and Diospyros conocarpa Gürke ex K. Schum. (Ebenaceae) were assessed. The phytochemical studies led to the isolation of eight compounds (1–8) from Diospyros conocarpa and six compounds (6, 9–13) from Antrocaryon klaineanum. These compounds were identified as mangiferolic acid (1), 3β, 22(S)-dihydroxycycloart-24E-en-26-oic acid (2), lupeol (3), aridanin (4), betulin (5), betulinic acid (6), bergenin (7), D-quercitol(8), entilin C(9), entilin A(10), antrocarine A(11), 7R,20(S)-dihydroxy-4,24(28)-ergostadien-3-one(12) and stigmasterol glucoside (13). The criteria for activity were set as follows: an IC50 value more than 10 μg/mL for crude extracts and more than 1 μg/mL for pure compounds. The hexane/ethyl acetate (1:1) fraction of A.klaineanum root bark (AKERF1) and the hexane/ethyl acetate (1:1) fraction of A.klaineanum trunk bark (AKETF1) presented the strongest antiplasmodial activities with IC50 values of 0.4 and 4.4 μg/mL, respectively. Aridanin (4) and antrocarine A(11), as well as the crude extract of D.conocarpa roots (EDCR), AKERF1 and AKETF1 showed moderate trypanocidal effects. The crude extract of A.klaineanum root bark (AKER) and AKETF1 exhibited attractive activities on HIV-1 integrase with IC50 values of 1.96 and 24.04 μg/mL, respectively. The results provide baseline information on the use of A.klaineanum and D.conocarpa extracts, as well as certain components, as sources of new antiplasmodial, antitrypanosomal and anti-HIV drugs.
- Full Text:
- Date Issued: 2019
A new indole alkaloid and other constituents from Monodora minor and Uvaria tanzaniae: their antitrypanosomal and antiplasmodial evaluation
- Christopher, Robert, Mgani, Quintino A, Nyandoro, Stephen S, Rousseau, Amanda L, Isaacs, Michelle, Hoppe, Heinrich C
- Authors: Christopher, Robert , Mgani, Quintino A , Nyandoro, Stephen S , Rousseau, Amanda L , Isaacs, Michelle , Hoppe, Heinrich C
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429347 , vital:72603 , xlink:href="https://doi.org/10.1080/14786419.2019.1710705"
- Description: Phytochemical investigation of the methanolic extract of Monodora minor Engl. and Diels (Annonaceae) stem bark yielded a new indole (E)-4-(1H-indol-5-yl)-but-3-en-2-one (1), a known indole 5-formyl-1H-indole (2) and an ubiquitous steroid sitosterol (3). The investigations of the methanolic extract of Uvaria tanzaniae Verdc. (Annonaceae) root bark yielded two previously reported C-benzylated dihydrochalcones namely uvaretin (4) and diuvaretin (5). Structures of the isolated compounds were elucidated based on NMR spectroscopy and high resolution electron ionization mass spectrometry (HR-EI-MS) data. All compounds were tested against Trypanosoma brucei brucei and Plasmodium falciparum. At a single concentration (20 μM) in the antitrypanosomal and antiplasmodial assays, compound 4 exhibited remarkable activities against T. brucei brucei and P. falciparum with percentage inhibition of 97.3% and 83.0% respectively, whereas compounds 1, 2, 3 and 5 were inactive. In a dose response antiplasmodial assay compound 4 exhibited moderate activity against P. falciparum with an IC50 value of 7.20 μM.
- Full Text:
- Date Issued: 2020
- Authors: Christopher, Robert , Mgani, Quintino A , Nyandoro, Stephen S , Rousseau, Amanda L , Isaacs, Michelle , Hoppe, Heinrich C
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429347 , vital:72603 , xlink:href="https://doi.org/10.1080/14786419.2019.1710705"
- Description: Phytochemical investigation of the methanolic extract of Monodora minor Engl. and Diels (Annonaceae) stem bark yielded a new indole (E)-4-(1H-indol-5-yl)-but-3-en-2-one (1), a known indole 5-formyl-1H-indole (2) and an ubiquitous steroid sitosterol (3). The investigations of the methanolic extract of Uvaria tanzaniae Verdc. (Annonaceae) root bark yielded two previously reported C-benzylated dihydrochalcones namely uvaretin (4) and diuvaretin (5). Structures of the isolated compounds were elucidated based on NMR spectroscopy and high resolution electron ionization mass spectrometry (HR-EI-MS) data. All compounds were tested against Trypanosoma brucei brucei and Plasmodium falciparum. At a single concentration (20 μM) in the antitrypanosomal and antiplasmodial assays, compound 4 exhibited remarkable activities against T. brucei brucei and P. falciparum with percentage inhibition of 97.3% and 83.0% respectively, whereas compounds 1, 2, 3 and 5 were inactive. In a dose response antiplasmodial assay compound 4 exhibited moderate activity against P. falciparum with an IC50 value of 7.20 μM.
- Full Text:
- Date Issued: 2020
Synthesis of N-Substituted phosphoramidic acid esters as “reverse” fosmidomycin analogues
- Adeyemi, Christiana M, Hoppe, Heinrich C, Isaacs, Michelle, Klein, Rosalyn, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447196 , vital:74591 , xlink:href="https://doi.org/10.1016/j.tet.2019.02.003"
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447196 , vital:74591 , xlink:href="https://doi.org/10.1016/j.tet.2019.02.003"
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
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