Mononuclear dioxomolybdenum(VI) thiosemicarbazonato complexes: Synthesis, characterization, structural illustration, in vitro DNA binding, cleavage, and antitumor properties

Mouayed A Hussein; Teoh S Guan; Rosenani A Haque; Mohamed B Khadeer Ahamed; Amin M S Abdul Majid

doi:10.1016/j.saa.2014.10.021

Mononuclear dioxomolybdenum(VI) thiosemicarbazonato complexes: Synthesis, characterization, structural illustration, in vitro DNA binding, cleavage, and antitumor properties

Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 5:136 Pt C:1335-48. doi: 10.1016/j.saa.2014.10.021. Epub 2014 Oct 22.

Authors

Mouayed A Hussein¹, Teoh S Guan², Rosenani A Haque¹, Mohamed B Khadeer Ahamed³, Amin M S Abdul Majid³

Affiliations

¹ School of Chemical Science, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
² School of Chemical Science, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Electronic address: sgteoh@usm.my.
³ EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.

PMID: 25456676
DOI: 10.1016/j.saa.2014.10.021

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.

Keywords: Antiproliferative activity; DNA binding; DNA cleavage; Molybdenum(VI) complexes; Thiosemicarbazone; X-ray crystal structure.

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Binding Sites / drug effects
Crystallography, X-Ray
DNA / chemistry
DNA / metabolism*
DNA Cleavage / drug effects*
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Molybdenum* / chemistry
Molybdenum* / pharmacokinetics
Oxides* / chemical synthesis
Oxides* / chemistry
Oxides* / pharmacokinetics
Thiosemicarbazones* / chemical synthesis
Thiosemicarbazones* / chemistry
Thiosemicarbazones* / pharmacokinetics

Substances

Antineoplastic Agents
Oxides
Thiosemicarbazones
molybdenum dioxide
Molybdenum
DNA
calf thymus DNA