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

Aim & background: Drugs with multiple bioactive moieties have the advantages of multiple modes of action and fewer chances of drug resistance. In continuation of our previous work of developing hybrid antimalarials, we present 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 1.49-13.49 mu M. The most promising hybrids (12d, 13a and 13c) may be good starting points for next-generation antimalarials.

Automated summary

In this study, two series of 7-chloroquinoline-sulfonamide hybrids were synthesized and evaluated for their antimalarial activity. The compounds demonstrated multiple modes of action and significant activity against Plasmodium falciparum. The most promising hybrids could be potential candidates for next-generation antimalarials.