Synthesis, antiplasmodial and antitrypanosomal evaluation of a series of novel 2-oxoquinoline-based thiosemicarbazone derivatives
- 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.
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Synthesis, in vitro cytotoxicity and trypanocidal evaluation of novel 1, 3, 6-substituted non-fluoroquinolones
- 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.
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