title: Piperine derivatives as potential inhibitors of Survivin: An in silico molecular docking.
abstract: Targeting Survivin, as an inhibitor of apoptosis and a regulator of cell division, has become a worldwide controversial issue. Piperine as a pungent alkaloid has been identified as the most potent adjuvant at enhancing the efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapies in triple-negative breast cancer (TNBC) cells in vitro and in vivo, which might be mediated through inhibition of Survivin. In this work, the binding energies, inhibition constants and binding modes of a group of previously synthesized Piperine derivatives at the binding site of Survivin have been studied using molecular docking tools and the best compounds with minimum binding energies are proposed as potential drugs for the inhibition of Survivin. A comprehensive SAR analysis has been done on the results that can be used for designing new Piperine analogs with higher efficacy. Molecular docking computations also show that the studied compounds can bind to BIR domain of Survivin in the same binding site as that of Smac/DIABLO with a suitable binding energy. This binding may result in the segregation of Smac/DIABLO in the cytosol and subsequently free Smac/DIABLO molecules could be available for binding with inhibitors of apoptosis to initiate caspase mediated apoptosis.
authors.affiliation: Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Sattarinezhad
authors.affiliation: Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran. Electronic address: bordbar@chem.ui.ac.ir.
authors.forename: Abdol-Khalegh
authors.initials: AK
authors.lastname: Bordbar
authors.affiliation: Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Fani
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D052117:Benzodioxoles / Q000737:chemistry*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D000077022:Survivin
chemical_list: D000470:Alkaloids; C107489:BIRC5 protein, human; D052117:Benzodioxoles; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D000077022:Survivin; C008922:piperine
keywords: Anticancer drug; Inhibitor; Molecular docking; Piperine; Survivin