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
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
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:
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