Low-dimensional compounds containing bioactive ligands. Part VI: Synthesis, structures, in vitro DNA binding, antimicrobial and anticancer properties of first row transition metal complexes with 5-chloro-quinolin-8-ol

• Published in: Journal of inorganic biochemistry 2016-01, Vol.154, p.67-77
• Main Authors: Potočňák, Ivan, Vranec, Peter, Farkasová, Veronika, Sabolová, Danica, Vataščinová, Michaela, Kudláčová, Júlia, Radojević, Ivana D., Čomić, Ljiljana R., Markovic, Bojana Simovic, Volarevic, Vladislav, Arsenijevic, Nebojsa, Trifunović, Srećko R.
• Format: Article
• Language: English
• Subjects: 5-Chloro-quinolin-8-ol complexes; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Cell Survival - drug effects; Chelating Agents - chemical synthesis; Chelating Agents - pharmacology; Chloroquinolinols - chemical synthesis; Chloroquinolinols - pharmacology; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Cytotoxicity; DNA - chemistry; DNA-binding properties; HCT116 Cells; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Microbial Viability - drug effects; Models, Molecular; Molecular Conformation; Topoisomerase I inhibition; Topoisomerase I Inhibitors - chemical synthesis; Topoisomerase I Inhibitors - pharmacology; Transition Elements - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.10.015

A series of new 3d metal complexes with 5-chloro-quinolin-8-ol (ClQ), [Mn(ClQ)2] (1), [Fe(ClQ)3] (2), [Co(ClQ)2(H2O)2] (3), [Ni(ClQ)2(H2O)2] (4), [Cu(ClQ)2] (5), [Zn(ClQ)2(H2O)2] (6), [Mn(ClQ)3]·DMF (7) and [Co(ClQ)3]·DMF·(EtOH)0.35 (8) (DMF=N,N-dimethylformamide), has been synthesized and characterized by elemental analysis, IR spectroscopy and TG–DTA thermal analysis. X-ray structure analysis of 7 and 8 revealed that these molecular complexes contain three chelate ClQ molecules coordinated to the central atoms in a deformed octahedral geometry and free space between the complex units is filled by solvated DMF and ethanol molecules. Antimicrobial activity of 1–6 was tested by determining the minimum inhibitory concentration and minimum microbicidal concentration against 12 strains of bacteria and 5 strains of fungi. The intensity of antimicrobial action varies depending on the group of microorganism and can be sorted: 1>ClQ>6>3/4>2>5. Complexes 1–6 exhibit high cytotoxic activity against MDA-MB, HCT-116 and A549 cancer cell lines. Among them, complex 2 is significantly more cytotoxic against MDA-MB cells than cisplatin at all tested concentrations and is not cytotoxic against control mesenchymal stem cells indicating that this complex seems to be a good candidate for future pharmacological evaluation. Interaction of 1–6 with DNA was investigated using UV–VIS spectroscopy, fluorescence spectroscopy and agarose gel electrophoresis. The binding studies indicate that 1–6 can interact with CT-DNA through intercalation; complex 2 has the highest binding affinity. Moreover, complexes 1–6 inhibit the catalytic activity of topoisomerase I. [M(ClQ)2] (M=Mn (1), Cu (5)), [Fe(ClQ)3] (2), [M(ClQ)2(H2O)2] (M=Co (3), Ni (4), Zn (6)), [Mn(ClQ)3]·DMF (7) and [Co(ClQ)3]·DMF·(EtOH)0.35 (8) (ClQ=5-chloro-quinolin-8-ol) were characterized by IR/UV–VIS spectroscopy, thermal analysis, crystallography (7, 8) and biological testing (1–6, ClQ) (antimicrobial activity, cytotoxicity, DNA binding, topoisomerase I inhibition). [Display omitted] •Eight 3d complexes with 5-chloro-quinolin-8-ol (ClQ) are characterized.•Complexes interact with DNA by intercalative binding mode.•Complexes target topoisomerase I as mildly effective topoisomerase inhibitors.•[Fe(ClQ)3] complex is highly active against human breast MDA-MB cancer cell line.•[Fe(ClQ)3] complex is not cytotoxic against control mesenchymal stem cells.