Structure‐Based Virtual Screening to Discover Potential Triazole Hits as an Anticancer Agents Targeting Telomerase Enzyme

Notably, around 85% of human cancer cases are reported to have increased expression of telomerase which is not observed in normal cells. This characteristic marks this protein as an attractive therapeutic target in cancer treatment. However, to date, there is no approved small molecule inhibitor available as a telomerase inhibitor. In the present study, a structure‐based virtual screening (SBVS) protocol was used to discover potential compounds from a library of 4042 triazole derivatives collected from the ChEMBL database. Initially, the database was screened for drug‐likeness and ADMET parameters. In SBVS, molecular docking studies identified 68 compounds having binding affinity greater than −10 kcal/mol, among 4042 triazole derivatives. Two compounds D443_1864 and D443_1840 were recognized as top raked hits with binding affinities −11.5 and −11 Kcal/mol, respectively. Both of these compounds were subjected to molecular dynamics studies at 100 ns. Compound D443_1864 was found to occupy the binding pocket more efficiently and formed a stable complex with telomerase enzyme. Compound D443_1864 showed lowest free energy of binding (∆G) −92.22 Kcal/mol molecular mechanics‐MM/GBSA studies. Overall, in this research, the compound D443_1864 was identified as a lead compound that can be further validated using in vitro studies and can be taken forward for anticancer drug development.