title: Carbohydrate linked organotin(IV) complexes as human topoisomerase Iα inhibitor and their antiproliferative effects against the human carcinoma cell line.
abstract: Dimethyltin(IV) complexes with ethanolamine (1) and biologically significant N-glycosides (2 and 3) were designed and synthesized. The structural elucidation of complexes 1-3 was done using elemental and spectroscopic methods; in addition, complex 1 was studied by single crystal X-ray diffraction studies. The in vitro DNA binding profile of complexes 2 and 3 was carried out by employing different biophysical methods to ascertain the feasibility of glycosylated complexes. Further, the cleaving ability of 2 and 3 was investigated by the agarose gel electrophoretic mobility assay with supercoiled pBR322 DNA, and demonstrated significantly good nuclease activity. Furthermore, both the complexes exhibited significant inhibitory effects on the catalytic activity of human Topo I at lower concentration than standard drugs. Computer-aided molecular docking techniques were used to ascertain the mode and mechanism of action towards the molecular target DNA and Topo I. The cytotoxicity of 2 and 3 against human hepatoma cancer cells (Huh7) was evaluated, which revealed significant regression in cancerous cells as compared with the standard drug. The antiproliferative activities of 2 and 3 were tested against human hepatoma cancer cells (Huh7), and results showed significantly good activity. Additionally, to validate the remarkable antiproliferative activity of complexes 2 and 3, specific regulatory gene expression (MMP-2 and TGF-β) was obtained by real time PCR.
authors: Department of Chemistry, Aligarh Muslim University, Aligarh - 202002, India. tsartaj62@yahoo.com.
authors: Rais Ahmad
authors: RA
authors: Khan
authors: Shipra
authors: S
authors: Yadav
authors: Zahid
authors: Z
authors: Hussain
authors: Farukh
authors: F
authors: Arjmand
authors: Sartaj
authors: S
authors: Tabassum
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D009947:Organotin Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009994:Osmolar Concentration; D010710:Phosphates / Q000737:chemistry; D011487:Protein Conformation; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D009947:Organotin Compounds; D010710:Phosphates; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human