Antiplasmodial activity of Hyptis pectinata extract and its analog against 3D7 Plasmodium falciparum through caseinolytic protease proteolytic (ClpP) inhibition

Abstract

Hyptolide and epoxy hyptolide were successfully isolated and synthesized from Hyptis pectinata extract that potential to cure malaria diseases. The previous studies showed that these compounds contained lactone groups associated with antibacterial and anticancer activities. However, the antimalarial activity remained unclear. This study aimed to investigate the antiplasmodial activity of H. pectinata extract, hyptolide, and epoxy hyptolide. These compounds were tested in vitro for antiplasmodial activity against chloroquinesensitive 3D7 strain of Plasmodium falciparum. Thin blood smears were used to assess the levels of parasitemia and growth inhibition of the isolates and the ClpP inhibition was analyzed under well diffusion assay. The results showed that hyptolide, epoxy hyptolide, and H. pectinata extracts potential inhibit proliferation of P. falciparum in doses-dependent manner with IC50 value of 2.06; 2.75; and 11.84 µg/ml, respectively. Further inhibition assay toward Pk-ClpP revealed that hyptolide (δ-lactone) more potent than β-lactone and PMSF demonstrated remarkably inhibition activity in doses-dependent manner. The results suggested that hyptolide exhibited antiplasmodial activity through Pk-ClpP inhibition and is potential to be developed as antimalarial drugs.