title: Mononuclear dioxomolybdenum(VI) thiosemicarbazonato complexes: Synthesis, characterization, structural illustration, in vitro DNA binding, cleavage, and antitumor properties.
abstract: Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with N-ethyl-2-(5-bromo-2-hydroxybenzylidene) hydrazinecarbothioamide (1), N-ethyl-2-(5-allyl-3-methoxy-2-hydroxybenzylidene) hydrazinecarbothioamide (2), N-methyl-2-(3-tert-butyl-2-hydroxybenzylidene) hydrazinecarbothioamide (3), and N-ethyl-2-(3-methyl-2-hydroxybenzylidene) hydrazinecarbothioamide (4). The molecular structures of 1, 2, and all the synthesized complexes were determined using single crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT-DNA) were investigated via UV, fluorescence titrations, and viscosity measurement. Gel electrophoresis revealed that all the complexes cleave pBR 322 plasmid DNA. The cytotoxicity of the complexes were studied against the HCT 116 human colorectal cell line. All the complexes exhibited more pronounced activity than the standard reference drug 5-fluorouracil (IC50 7.3μM). These studies show that dioxomolybdenum(VI) complexes could be potentially useful in chemotherapy.
authors.affiliation: School of Chemical Science, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Mouayed A
authors.initials: MA
authors.lastname: Hussein
authors.affiliation: School of Chemical Science, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Electronic address: sgteoh@usm.my.
authors.forename: Teoh S
authors.initials: TS
authors.lastname: Guan
authors.affiliation: School of Chemical Science, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Rosenani A
authors.initials: RA
authors.lastname: Haque
authors.affiliation: EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.affiliation: EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Amin M S
authors.initials: AM
authors.lastname: Abdul Majid
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry / Q000493:pharmacokinetics; D010087:Oxides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D010087:Oxides; D013882:Thiosemicarbazones; C539565:molybdenum dioxide; D008982:Molybdenum; D004247:DNA; C427203:calf thymus DNA
keywords: Antiproliferative activity; DNA binding; DNA cleavage; Molybdenum(VI) complexes; Thiosemicarbazone; X-ray crystal structure