title: New modulated design, docking and synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV complex as potential topoisomerase II inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines.
abstract: New carbohydrate-conjugate heterobimetallic complexes [C₂₂H₅₀N₆O₁₃CuSnCl₂] (3) and [C₂₂H₅₈N₆O₁₇NiSnCl₂] (4) were synthesized from their monometallic analogs [C₂₂H₅₂N₆O₁₃Cu] (1) and [C₂₂H₆₀N₆O₁₇Ni] (2) containing N-glycoside ligand (L). In vitro DNA binding studies of L and complexes (1-4) with CT DNA were carried out by employing various biophysical and molecular docking techniques which revealed that heterobimetallic complex 3 strongly binds to DNA in comparison to 4, monometallic complexes (1 and 2) and the free ligand. Complex 3 cleaves pBR322 DNA via hydrolytic pathway (confirmed by T4 DNA ligase assay) and inhibited Topo-II activity in a dose-dependent manner. Furthermore, complex 3 was docked into the ATPase domain of human-Topo-II in order to probe the possible mechanism of inhibition.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: tsartaj62@yahoo.com.
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Farukh
authors.initials: F
authors.lastname: Arjmand
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D006801:Humans; D066298:In Vitro Techniques; D062105:Molecular Docking Simulation; D013057:Spectrum Analysis; D014001:Tin / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D002241:Carbohydrates; D059005:Topoisomerase II Inhibitors; D014001:Tin; D003300:Copper; D004247:DNA
keywords: DNA cleavage; Heterobimetallic complexes; Molecular docking; T4 ligase