title: Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: in vitro DNA binding, pBR322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines.
abstract: New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO₃)₂ (1) and [Zn(phen)L](NO₃)₂ (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI₅₀ values < 10 μg/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out.
authors: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: tsartaj62@yahoo.com.
authors: Sartaj
authors: S
authors: Tabassum
authors: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors: Mehvash
authors: M
authors: Zaki
authors: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors: Mohd
authors: M
authors: Afzal
authors: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors: Farukh
authors: F
authors: Arjmand
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000009:adverse effects*; D004587:Electrophoresis, Agar Gel; D006801:Humans; D062105:Molecular Docking Simulation; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D013057:Spectrum Analysis / Q000379:methods; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D059004:Topoisomerase I Inhibitors; D003300:Copper; D004247:DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: Anticancer activity; DNA cleavage; In vitro DNA binding; Molecular docking; Topo-I inhibition