Oxime functionalized Chalcones: Unveiling a new class of Chalcones with potent Antiplasmodial activity against blood-stages of Plasmodium falciparum in culture

Abstract

The Plasmodium falciparum parasite, which is responsible for malaria, has developed resistance to several first-line antimalarial drugs. To address this issue, researchers have been developing novel hybrid molecules that can inhibit parasite growth. In this study, a total of 38 chalcone oxime ethers, consisting of four different types, were evaluated for in vitro blood-stage antiplasmodial activity against P. falciparum (3D7) using SYBR green I assay. The four classes of oxime ethers showed promising to moderate antiplasmodial activity. At least one molecule from each class was potent, with the IC₅₀ values of less than 5 μg/mL. Among the four classes, chalcone-chalconeoxime ethers (CCOE) were the most effective, with the IC₅₀ values of 1.55 μg/mL and 1.4 μg/mL for CCOE-2 and CCOE-5, respectively. The most potent molecules, CKOE-13, COAE-2, CCOE-2, and CCOE-5, were tested against the chloroquine-resistant strain P. falciparum (INDO) exhibited IC₅₀ values of less than 5 μg/mL. Notably, the most potent molecules did not induce hemolysis at concentrations up to 50 μg/mL. These findings highlight a new class of chalconeoxime ethers as potent antiplasmodial agents, warranting further exploration of their biological activities.