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 parasitic growth. A total of 38 chalcone oxime ethers, consisting of four different types, were used for in vitro blood-stage antiplasmodial evaluation against P. falciparum (3D7). The four classes of oxime ethers showed promising to moderate antiplasmodial activity. At least one molecule from each class was potent, with IC₅₀ values of less than 5 μg/mL. Among the four classes, chalcone-chalconeoxime ethers (CCOE) were the most effective, with 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) and exhibited IC₅₀ values of less than 5 μg/mL. Notably, the most potent molecules did not induce hemolysis at concentrations of up to 25 μg/mL. These findings highlight a new class of chalconeoxime ethers as potent antiplasmodial agents, warranting further exploration of their biological activities.