- Title
- Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers.
- Creator
- 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
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/122908
- Identifier
- vital:35370
- Identifier
- 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.
- Format
- 10pages, pdf
- Language
- English
- Relation
- ChemMedChem, Lunga, M.J., Chisango, R.L., Weyers, C., Isaacs, M., Taylor, D., Edkins, A.L., Khanye, S.D., Hoppe, H.C. and Veale, C.G., 2018. Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-thanone Ethers and Thioethers. ChemMedChem, 13(13), pp.1353-1362., ChemMedChem number 23 1355 1362 13 May 2018 2040-2511
- Rights
- ChemMedChem
- Rights
- Use of this resource is governed by the terms and conditions of the Wiley Online Library Terms of Use Statement (https://onlinelibrary.wiley.com/terms-and-conditions)
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Collections
Edkins, Adrienne Lesley (Associate Prof)
Veale, Clinton G L (Dr)
Khanye, David Setshaba (Associate Prof)
RU Centre for Chemico- and Biomedicinal Research (CCBR)
Hoppe, Heinrich C (Prof)
Isaacs, Michelle (Mrs)
RU Department of Pharmacy
SDG 03. Good Health and Well-Being
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