Synthesis and Biological Evaluation of 2-(3-((2-(2-(Quinoline-4-yloxy)acetyl)-hydrazineylidene)methyl)-1H-indol-1-yl)acetamide Derivatives as Antiprotozoal Agent: In silico Molecular Docking Study

Abstract

In an unremitting search for potential antiprotozoal agents, a series of 2-(3-((2-(2-(quinolin-4-yloxy)acetyl)hydrazineylidene)methyl)-1H-indol-1-yl)acetamide derivatives (QC1-QC11) was designed, synthesized, characterized and evaluated for its antiprotozoal activities. The anti-amoebic activity of these synthesized compounds was assessed against the HM1:IMSS strain of Entamoeba histolytica. All the compounds exhibited good to potent activity with IC50 values in the range of 0.36-30.94 µM and metronidazole (MTZ) was taken as standard (IC50 = 1.8 µM). Compound QC4 was recorded with lowest IC50 value (0.36 µM). Antimalarial screening against Plasmodium falciparum strain (NF54) revealed the poor efficacy of these compounds. Derivatives QC2 and QC4 exhibited a slight inhibitory effect on the malaria parasite compared to quinine, while showing negligible impact on red blood cell integrity. Of all the derivatives, QC4 displayed general toxicity to all the organisms and cells used in this study, with QC2 showing minimal toxicity to these biological systems. The docking study of these derivatives indicated the promising binding affinity when interacted with enzyme EhTHRase (PDB id: 3D8X). QC6 recorded with most negative binding free energy value (-8.9 kcal/mol) showing strongest interaction while QC4 also had promising interaction with binding free energy -8.7 kcal/mol, hence, these derivatives are found to be promising anti-amoebic agents.