Synthesis, X-ray crystal structure and biological evaluation of zinc(II)-dichlorido complexes with 9-deazahypoxathine derivatives

A series of mononuclear zinc(II)-dichlorido complexes of the general formula [Zn(L-n)(2)Cl-2]center dot Solv (1-5); n = 1-5, Solv = CH3CN for 1, 2CH(3)CN for 1b, 1/2H(2)O for complexes 2 and 4; containing 9-deazahypoxanthine derivatives (L-n, 6-(omega-alkyl) oxy-9-deazapurine derivatives) was prepared and thoroughly characterized (by elemental analysis, ESI+ mass spectrometry, FT-IR and multinuclear NMR spectroscopy, and TG/DTA analysis). Single crystal X-ray analysis of [Zn(L-1)(2)Cl-2]center dot 2CH(3)CN (1b) revealed a distorted tetrahedral geometry in the vicinity of the zinc(II) atom with two 6-ethoxy-9-deazapurine molecules (L-1) coordinated through the N3 atoms. The complexes were screened for their in vitro antitumor activity against three human cancer cell lines, PC3 and LNCaP (prostate carcinoma), and A2780 (ovarian carcinoma). Moreover, the ability of the complexes to modulate the secretion of interleukin IL-1 beta and matrix metalloproteinase MMP-2 activity on a lipopolysaccharide (LPS)-activated macrophage-like THP-1 cell model was evaluated. The results revealed that the zinc(II) complexes show no in vitro cytotoxicity within the range of 0.01-50 mu M on PC3, LNCaP and A2780 cell lines. The ability of the complexes to decrease the IL-1 beta production was not observed. On the other hand, these complexes were able to enhance the total amount of MMP-2 protein and significantly elevate the level of the active form of this protease. (C) 2015 Elsevier B.V. All rights reserved.