Abstract
M.Sc. (Chemistry)
According to the 2017 World Health Organization (WHO) report, an estimated 216 million cases of malaria occurred worldwide and malaria infection was responsible for an estimated 445 000 deaths globally and 90% of those being in Africa followed by 7% in South-East Asia and 2% of the deaths occurring in the Eastern Mediterranean. Seventy percent of these deaths occurred in children under the age of 5 years. Recently, WHO prescribed a diagnosis artemisinin-based combination therapy which focuses on either delaying or preventing the development of drug resistance. Even though implementation of curative and preventative measures has been done without clinical resistance against artemisinin, recent report from South-East Asia converge towards tolerance which may lead to resistance against this class of drugs. Sulfadoxine-pyrimethamine and chloroquine have been the pinnacle drug since 1970s, undermining malaria control efforts and reversing gains in child survival. Despite the advantageous quality posed by these drugs exemplified by limited host toxicity, low cost, effective and well defined synthesis protocols, resistance of Plasmodium. falciparum has been a recurring problem.
Moreover, the emergence of artemisinin resistant strains of malaria necessitates the discovery for new chemo-types with novel mechanism of action. Inclined to this limelight, our group unveiled the synthesis and antimalarial evaluation of novel thiochromans as new chemo-types. The study revealed that carbohydrate based thiochromans with bulky and lipophilic groups on the aromatic ring of the thiochroman moiety (especially the sulfone chemotype) exhibits promising activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (FCR3) strains with IC50 values of 0.3-0.4 μM. Literature reported that replacing the sulfoxide/sulfone (66 and 73) moieties of biologically active compounds with sulfoximine exhibited improved potency. Therefore, it was hoped that better activity would be obtained by the introduction of the sulfoximine chemotype into the carbohydrate derived thiochromans...