Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of<i>Plasmodium falciparum</i>at the trophozoite stage

Abstract

Falcipain-2 (FP2) is a papain family cysteine protease and a key member of the hemoglobin degradation pathway, a process that is required at erythrocytic stages of <i>Plasmodium falciparum</i> to obtain amino acids. In this study, we report a set of 10 quinoline-triazole-based compounds (T1-T10) which exhibit a good binding affinity for FP2, inhibit its catalytic activity at micromolar concentrations and thereby arrest the parasite growth. Compounds T4 and T7 inhibited FP2 with IC₅₀ values of 16.16 μM and 25.64 μM respectively. Both the compounds T4 and T7 arrested the development of <i>P. falciparum</i> at the trophozoite stage with an EC₅₀ value 21.89 μM and 49.88 μM. These compounds also showed morphological and food-vacuole abnormalities like E-64, a known inhibitor of FP2. Our results thus identify the quinoline-triazole-based compounds as a probable starting point for the design of FP2 inhibitors and they should be further investigated as potential antimalarial agents.