Synthesis, Molecular Docking and Antiamoebic Studies of Nitroimidazole-Indole Conjugate - Abstract
In an imperative search for efficacious antiamoebic agents nitroimidazoles-indole conjugates were synthesized, characterised and biologically tested for HM1: IMSS strain of E. histolytica. Designing of conjugates by linking two scaffolds with different intrinsic properties can give remarkable results. Molecular docking studies showed the key interacting active residues in the binding site of E. histolytica O-acetyl-serine Sulfohydroylase protein (EhOASS) recommended that the addition of a hydrophobic group better fit within enzyme active site leading to enhanced inhibitory activity. All the compounds were less toxic against HeLA cervical cancer cell line. The compounds RC6, RC8, RC9 and RC10 exhibited strong inhibitory activities, with IC50 values of 3.61, 2.08, 1.75, and 1.22mM E. histolytica O-acetyl-serine Sulfohydroylase protein (EhOASS) in vitro respectively. The promising antiamoebic activity and enzymatic assay of RC6, RC8, RC9 and RC10 make them promising molecules for further lead optimization in the development of novel antiamoebic agents.