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

• Published in: Future medicinal chemistry Vol. 14; no. 23; pp. 1725 - 1739
• Main Authors: Batra, Neha, Agarwal, Drishti, Wadi, Ishan, Tekuri, Chandra Sekhar, Gupta, Rinkoo D, Nath, Mahendra
• Format: Journal Article
• Language: English
• Published: England Newlands Press Ltd 01-12-2022
• Subjects: 1,3-dipolar cycloaddition; 7-chloroquinoline; [1,2,3]-triazoles; antimalarials; Antimalarials - pharmacology; click reaction; cytotoxicity; DBSA; Plasmodium falciparum; Structure-Activity Relationship; sulfonamide; Sulfonamides - pharmacology; synthesis; Triazoles - pharmacology; synthesis; DBSA; click reaction; sulfonamide; antimalarials; 7-chloroquinoline; cytotoxicity; 1,3-dipolar cycloaddition; [1,2,3]-triazoles
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2022-0187

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.
The first series of compounds were synthesized by using
-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.
The majority of these compounds demonstrated noncytotoxicity and significant antimalarial activity against
(3D7) with IC
values in the range of 1.49–13.49 μM. The most promising hybrids (
,
and
may be good starting points for next-generation antimalarials.