Cytotoxic, DNA binding and drug reservoir property of Pt(II)–sulfur complexes: In-vitro kinetics, mechanism with bio-relevant molecules in aqueous medium and a theoretical approach. (24th November 2016)

• Record Type: Journal Article
• Authors: Mukherjee, Subhajit; Mitra, Ishani; Reddy B., Venkata P.; Mahata, Sujay; Bose K., Jagadeesh C.; Dasgupta, Subrata; Linert, Wolfgang; Ch. Moi, Sankar
• Is Part Of: Polyhedron. Volume 119(2016)
• Page Start: 84
• Page End: 97
• Publication Date: 2016-11-24
• Subjects: Pt(II) complexes -- Kinetics and mechanism -- DFT-study -- DNA-binding -- Cytotoxicity; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2016.08.024
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical Abstract: Cytotoxicity and DNA binding property of the synthesised Pt(II) complexes were assessed. Pt(II)–sulfur chelation and their drug reservoir mechanism was studied by kinetic investigation. Abstract: Synthesis and cytotoxic property of Pt(II)–sulfur complexes are significant in biological aspect. In order to investigate their relevance, two sulfur chelated model complexes are considered for detailed study. In-vitro drug reservoir property of the complex [Pt(MAMP)(H2 O)2 ]X2 2 (where, MAMP = 2-[(N-methylamino)methyl]pyridine and X = NO3 − or ClO4 − ) in model reactions with sulfur containing bio-molecules dl-methionine (dl-meth) and dl-penicillamine (dl-pen) are studied to explore the 'drug reservoir' mechanism. The complex [Pt(MAMP)(dl-meth)]3 and [Pt(MAMP)(dl-pen)]4 are synthesized from complex2, which is obtained from the hydrolysis of complex [Pt(MAMP)Cl2 ]1 and characterized by spectroscopic methods. Interaction mechanism between complex2 with dl-meth and dl-pen has been established by kinetic study. Two step consecutive reaction rate constants ( k 1 and k 2 ) and corresponding activation parameters (Δ H ‡ and Δ S ‡ ) for both the steps are calculated and an associative mechanism is proposed. Theoretical investigations like structural optimization, HOMO–LUMO energy calculations, NBO analysis have been performed. The coordination mode of dl-meth and dl-pen via (S, O) are established by spectroscopic methods and confirmed by NBO analysis. DNA binding property of the complexes2 –4 has been investigated by UV–Vis spectra, competitive binding experiment, gel electrophoresis and their corresponding binding constants ( k b and k sv ) are calculated. The computational molecular docking study is carried out for the complexes with B-DNA to confirm their DNA binding mode. Cytotoxic property of the complexes3 and4 are investigated on HeLa and HepG2 cell lines and also been compared with complex2 and well known anticancer drug cis platin and their corresponding IC50 values are calculated.