Computational study of curcumin analogues by targeting DNA topoisomerase II: a structure-based drug designing approach

Curcumin, a golden yellow pigment present in the spice turmeric, has pleiotropic chemopreventive and therapeutic active compound against many diseases including cancer. It has been reported that curcumin acts as a topoisomerase II inhibitor and it was found that even concentration of 50 µM of curcumin in vitro is active in a similar fashion as etoposide (antineoplastic agent). Topoisomerases (type I and type II) are enzymes that regulate the overwinding or underwinding of DNA by cutting the phosphate bond of one or two strands of DNA, respectively. Topoisomerase II was selected as target, since it affects both strands of DNA. The present in silico study about designing curcumin analogues as better inhibitors of topoisomerase vis-à-vis curcumin is based on ADME filtering and docking simulation using Schrödinger suite. The docking simulation result suggested that out of 1000 designed curcumin analogues using ligbuilder tool and curcumin as a lead, 293 screened analogues show good binding affinity at the active site of Human DNA topoisomerase II in comparison to known drug Salvicine. The top five analogues with best binding affinity was shown by ligand1_826, ligand1_758, ligand1_976, ligand1_956 and ligand1_827 with glide scores − 16.70, − 16.03, − 15.45, − 15.43 and − 15.09, respectively. Therefore it is possible that screened curcumin analogues can be used as lead molecules for screening of ligand database and future chemopreventive agents.