SYNTHESIS AND ANTIPLASMODIAL ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES
Abstract
Increased drug resistance in malaria toward many of the existing antimalarials make the condition worse. Hence, indicates the necessity of the
novel molecules to overcome the problem. A series of chalcone derivatives (3a-4e) were primed via Claisen-Schmidt condensation of substituted
aldehydes with substituted methyl ketones. These derivatives were tested against Plasmodium falciparum clinical isolate for their antiplasmodial
activity. Furthermore, in-vitro β-hematin formation assay has been conducted in order to gain insight into the possible mechanism of action. Out
of the 10 synthesized compounds, two compounds 4a and 4d exhibited promising antiplasmodial activities (50% inhibitory concentration [IC50]
values 7.45±0.65 and 6.01±0.29 μg/ml, respectively). Other compounds (3a, 4b, 4e and 3d) showed moderate inhibition against P. falciparum. Among
all the compounds, 4a showed good hemozoin inhibitory activity (IC50 - 19.75 μg/ml) while 3a and 4d showed moderate type inhibition. These
molecules may act as templates for medicinal chemistry to discover novel and hybrid molecules with improved characteristics, which may become
future candidates for the treatment of malaria.
Keywords: Chalcone, Malaria, Plasmodium falciparum, β-hematin.
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