Abstract
Malaria is a disease that continues to claim the lives of millions of people in the tropical regions of developing countries and more specially the sub-Saharan countries of Africa. The disease is transmitted by infected female Anopheles mosquito which can transmit Plasmodium parasites. There are many Plasmodium species, however, there are only four species of the malarial parasites which can infect humans, namely P. falciparum, P. vivax, P. ovale and P. malariae. P. falciparum is the main species that causes severe cases and deaths.
Among others chloroquine used to be the most effective drug to treat malaria. However, due to the emergence of drug resistant strains, WHO introduced ACTs (Artemisinin Combination Therapies) as a gold-standard malaria treatment. ACTs combine artemisinin or its derivatives with other anti-malaria drugs. ACTs have high killing rates of Plasmodium parasites and also reduces anti-plasmodium drug resistances. However, with reports indicating the emergence of artemisinin resistant strains of P. falciparum and the fact that artemisinin being the last line of defense, the search for the development of new antimalarial chemotypes with novel mode of action will be ideal.
In this regard, our group introduced carbohydrate-derived thiochroman derivatives as new antimalarial chemo-types. The structural activity relationship studies indicated that the presence of sulfur in high oxidation state (sulfone), benzyl protecting groups on the sugar moiety and a tert-butyl substituent on the aromatic ring of the thiochroman unit were important features to render high antiplasmodial activities. In the hope of improving the IC50 values to lower nanomolar concentrations, several sulfone derivatives with various carbohydrate stereoisomers and thiophenols possessing alkyl chains of various chain lengths and steric sizes were successfully synthesized and evaluated for their antiplasmodial activities. However, none of them led to improved IC50 values. The inability of the sulfone functional group for further derivatization in order to synthesize...
M.Sc. (Chemistry)