N‐Substituted Bridged Azaozonides as Promising Antimalarial Agents

• DOI: 10.1002/cmdc.202500181
• Publication Date: 2025-04-17T12:37:16Z
• Authors: Paolo Coghi; Ivan A. Yaremenko; Parichat Prommana; Ali Adnan Nasim; Yulia Yu. Belyakova; Ruihong Chen; Peter S. Radulov; Chairat Uthaipibull; Alexander O. Tere...; Vincent Kam Wai Wong
• Keywords: IC50; Antimalarial Agent

Forty‐five aminoperoxides belonging to bridged azaozonides, N‐substituted and tricyclic were evaluated for in vitro antimalarial activity against Plasmodium falciparum (3D7) cytotoxicity immortalized human normal liver (LO2) lung (BEAS‐2B) cell lines, as well (HepG2) (A549) cancer lines. Seven azaozonides exhibited high the chloroquine‐sensitive 3D7 strain of P. falciparum, with IC50 < 1 µM. The lead compound 22 showed = 0.07 µM selectivity index 1428. Most generally non‐cytotoxic both cells. Only two moderate on HepG2 line (2: 4.12 µM, 40: 9.95 µM), while one azaozonide 2 had an 5.56 A549 line. From this small library 45 aminoperoxides, was found have comparable artemisinin chloroquine used medical practice. These findings provide a new source developing agents through structural modification aminoperoxide compounds.