Molecular interaction of the downstream executioner cysteine aspartyl proteases (Caspase-3 and caspase-7) with corilagin, quercetin, rutin, kaempferol, gallic acid, and geraniin of acalypha wilkesiana müll.arg.

Abstract

Apoptosis is caused by activation of caspases, i.e. intracellular cysteine proteases which cleave their substrates at aspartic acid residues. Caspases are categorized into (1) the initiator caspases (caspase-9) and (2) the executioner caspases (caspases-3 and-7). The ethanolic extract of Acalypha wilkesiana Müll.Arg suppressed the growth of human breast cancer cell lines and showed cytotoxicity against cervical cancer cell lines and human skin keratinocyte cell lines. Our work studied the structure-based molecular interaction of the caspases and this plant. The X-ray crystal structure of human caspase-3 and-7 were downloaded from https://www. rcsb.org/structure/. The ligands were built using LigandScout software and were subjected to energy minimization using the molecular mechanic forcefield partial charges in LigandScout. The energy-minimized ligands were docked to caspase-3 and caspase-7. The results indicated that kaempferol possesses a similar binding mode in terms of hydrogen bond (Arg64, Gln161, His121, Tyr204 in caspase-3; Cys290 in caspase-7) and hydrophobic interaction (Trp206 in caspase-3; Tyr223, Phe221, Ile183, Val292 in caspase-7), with that of the caspase substrate with better affinity. The binding mode of rutin resembles that of 2-(2,4 dichloro phenoxy)-N-(2-mercapto-ethyl)-acetamide in caspase-7 with better affinity. In conclusion, kaempferol, and rutin, two flavonoids in Acalypha wilkesiana Müll. Arg might be able to inhibit the downstream executioner caspases, particularly caspase-3 and caspase-7. The binding affinity of these compounds against caspases is better than the standards.