Synthesis and antimalarial activity of 7-chloroquinoline-tethered sulfonamides and their [1,2,3]-triazole hybrids.

Abstract

Aim & background: Drugs with multiple bioactive moieties have the advantages of multiple modes of action and fewer chances of drug resistance. In continuation of ourprevious work of developing hybrid antimalarials, wepresent herein the synthesis and antimalarial activity of two different series of 7-chloroquinoline-sulfonamide hybrids. Materials & methods: The first series of compounds were synthesized by using p-dodecylbenzenesulfonic acid as a Bronsted acid catalyst in ethanol. The second series' compounds were synthesized by 1,3-dipolar cycloaddition of azides and alkynes under click reaction conditions. Results & conclusion: The majority of these compounds demonstrated noncytotoxicity and significant antimalarial activity against Plasmodium falciparum (3D7) with IC50 values in the range of 1.49-13.49μM. The most promising hybrids (12d, 13a and 13c) may be good starting points for next-generation antimalarials.