Synthesis, characterization and biological evaluation of Co(III) complexes with quinolone drugs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00504494" target="_blank" >RIV/68081707:_____/19:00504494 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/19:73597251

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0162013418306238?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0162013418306238?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jinorgbio.2019.01.005" target="_blank" >10.1016/j.jinorgbio.2019.01.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis, characterization and biological evaluation of Co(III) complexes with quinolone drugs

Popis výsledku v původním jazyce

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)center dot 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 pi-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 (MRCS 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.

Název v anglickém jazyce

Synthesis, characterization and biological evaluation of Co(III) complexes with quinolone drugs

Popis výsledku anglicky

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)center dot 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 pi-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 (MRCS 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA18-09502S" target="_blank" >GA18-09502S: Ovlivnění rezistence nádorových buněk k chemoterapii s cílem obnovit jejich citlivost k novým, existujícím a dosud neúspěšným metalofarmakům</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Inorganic Biochemistry

ISSN

0162-0134

e-ISSN

—

Svazek periodika

193

Číslo periodika v rámci svazku

APR 2019

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

94-105

Kód UT WoS článku

000462416600011

EID výsledku v databázi Scopus

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