Synthesis, characterization and biological evaluation of Co(III) complexes with quinolone drugs
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30703748
DOI
10.1016/j.jinorgbio.2019.01.005
PII: S0162-0134(18)30623-8
Knihovny.cz E-resources
- MeSH
- Anti-Bacterial Agents chemical synthesis pharmacology toxicity MeSH
- Quinolones chemical synthesis pharmacology toxicity MeSH
- Ciprofloxacin pharmacology MeSH
- DNA Gyrase metabolism MeSH
- DNA metabolism MeSH
- Topoisomerase II Inhibitors chemical synthesis pharmacology toxicity MeSH
- Intercalating Agents chemical synthesis pharmacology toxicity MeSH
- Cobalt chemistry MeSH
- Coordination Complexes chemical synthesis pharmacology toxicity MeSH
- Humans MeSH
- Ligands MeSH
- Microbial Sensitivity Tests MeSH
- Cell Line, Tumor MeSH
- Cattle MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- calf thymus DNA MeSH Browser
- Quinolones MeSH
- Ciprofloxacin MeSH
- DNA Gyrase MeSH
- DNA MeSH
- Topoisomerase II Inhibitors MeSH
- Intercalating Agents MeSH
- Cobalt MeSH
- Coordination Complexes MeSH
- Ligands MeSH
Nine novel cobalt(III) ternary complexes bearing 4N donor ligands (tris(2-aminoethyl)amine (tren) or tris(2-methylpyridyl)amine (tpa)) and (fluoro)quinolones (quinH) with antibacterial and potential antitumor activity have been synthesized, characterized and screened in various biological assays. The molecular structures of [Co(tpa)(nal)](PF6)2 (3) and [Co(tpa)(nor)(Co(tpa)(norH)](PF6)3(Cl)2∙5MeOH (8) (nal = deprotonated form of nalidixic acid, norH = norfloxacin) with the expected octahedral geometry and (O,O) coordination of the quinolone ligands are also reported. Cyclic voltammetric studies revealed that the 4N donor ligands have much higher effect on the reduction potential of these ternary complexes than the quinolones. Due to the π-back-bonding interaction of the metal ion with the pyridyl-N atoms, the tpa containing compounds demonstrated lower stability and were easier to get reduced in a reversible manner. This character makes them unlikely candidates for development of effective, highly selective hypoxia-activated pro-drug complexes, but this goal might be achieved by substitution of tpa by tren. [Co(tren)(cip)](PF6)2 (4) and [Co(tpa)(cip)](PF6)2 (5) (cip = deprotonated form of ciprofloxacin) showed slightly less antibacterial activity against Escherichia coli than free ciprofloxacin (cipH) and they found to have very low toxicity towards both selected cancer (HeLa, MCF 7, MDA-MB-239) and noncancerous (MRC5 pd30) cells. Interaction of 4 and 5 with calf thymus DNA studied by UV-Vis, flow linear dichroism, viscometry and DNA melting indicated the complexes to bind to DNA as intercalators. DNA electrophoresis revealed that, unlike Co(II) complexes, 4 and 5 are not capable of cleaving DNA, but they can inhibit bacterial DNA gyrase 5 being slightly more active than 4.
Department of Biophysics Palacky University Slechtitelu 27 78371 Olomouc Czech Republic
Department of Physical Chemistry University of Debrecen H 4032 Debrecen Egyetem tér 1 Hungary
Institute of Biophysics Czech Academy of Sciences Kralovopolska 135 61265 Brno Czech Republic
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