Platinum(II)-azoimidazole drugs against TB and cancer: Structural studies, cytotoxicity and anti-mycobacterial activity

Abstract

1-Alkyl-2-(arylazo)imidazoles (Haai-C4H9 (1), Haai-C10H21 (2)) and their Pt(II) complexes, [Pt(Haai-C4H9)Cl-2] (3) and [Pt(Haai-C10H21)Cl-2] (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 H37Ra (ATCC 25177) and H(37)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-C10H21)Cl-2] (4), is less efficient due to hydrophobic interactions than the lower homologue [Pt(Haai-C4H9)Cl-2] (3) (K-b(3), 5.9(2) x 10(6) M-1 and molar volume, 276.03(10) cm(3) mol(-1); [Pt(Haai-C10H21)Cl-2], K-b(4), 5.86(2) x 10(5) M-1 and molar volume, 397.56(8) cm(3) mol(-1)). (C) 2018 Elsevier Ltd. All rights reserved.