Platinum(II)-azoimidazole drugs against TB and cancer: Structural studies, cytotoxicity and anti-mycobacterial activity. (15th September 2018)

• Record Type: Journal Article
• Authors: Sen, Chandana; Patra, Chiranjit; Mondol, Sudipa; Datta, Amitabha; Mallick, Debashis; Mondal, Tapan Kumar; Askun, Tulin; Celikboyun, Pinar; Cantürk, Zerrin; Sinha, Chittaranjan
• Is Part Of: Polyhedron. Volume 152(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-09-15
• Subjects: DNA deoxyribo nucleic acid -- DMSO dimethyl sulfoxide -- CFU colony forming units -- MBC minimum bactericidal concentration -- MIC minimum inhibitory concentration -- ORTEP oak ridge thermal ellipsoid plot; Platinum(II)-arylazoimidazoles -- X-ray structure -- Cytotoxicity -- Antibacterial activity -- DNA interaction; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2018.05.062
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical abstract: The complexes [Pt(Raai-Cn H2n+1 )Cl2 ] (Raai-Cn H2n+1, 1-alkyl-2-(arylazo)imidazole)) have been characterized and evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37 Ra and H37 Rv strains. Cytotoxic effects on three cancer cell lines, A549, MCF-7 and CACO-2, and one normal cell line, 3T3, have been examined. The DNA interaction of the complexes shows that the binding efficiency decreases with increasing molecular dimension and chain length of Cn H2n+1 in the complexes. Docking is used to explain the interaction. Abstract: 1-Alkyl-2-(arylazo)imidazoles (Haai-C4 H9 (1 ), Haai-C10 H21 (2 )) and their Pt(II) complexes, [Pt(Haai-C4 H9 )Cl2 ] (3 ) and [Pt(Haai-C10 H21 )Cl2 ] (4 ) were synthesized and characterized by different spectroscopic studies and structural confirmation has been achieved in the case of complex 3 by single crystal X-ray diffraction analysis. Complexes 3 and 4 were evaluated for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37 Ra (ATCC 25177) and H37 Rv (ATCC 25618) strains, as well as against two clinical strains. Their cytotoxic effects on three cancer cell lines, A549 (human lung carcinoma), MCF-7 (human breast cancer) and Caco-2 (colorectal adenocarcinoma line), and one normal cell line, 3T3 (mouse normal fibroblast) were examined. The DNA interaction of the complexes shows that the intrinsic binding constant ( K b ) decreases with the increasing molecular dimension and the chain length of the 1-alkyl group. The longer 1-alkyl chain substituted complex, [Pt(Haai-C10 H21 )Cl2 ] (4 ), is less efficient due to hydrophobic interactions than the lower homologue [Pt(Haai-C4 H9 )Cl2 ] (3 ) ( K b (3 ), 5.9(2) × 10 6 M −1 and molar volume, 276.03(10) cm 3 mol −1 ; [Pt(Haai-C10 H21 )Cl2 ], K b (4 ), 5.86(2) × 10 5 M −1 and molar volume, 397.56(8) cm 3 mol −1 ).