Synthesis, antimicrobial evaluation and molecular modeling of 5-hydroxyisoquinolinium salt series; the effect of the hydroxyl moiety

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F16%3AA20020XO" target="_blank" >RIV/61988987:17110/16:A20020XO - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61988987:17110/15:A1668187 RIV/60162694:G44__/16:43875554 RIV/62690094:18450/16:50004667 RIV/00216208:11160/16:10319845 a 2 dalších

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0968089616300050?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0968089616300050?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2016.01.006" target="_blank" >10.1016/j.bmc.2016.01.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis, antimicrobial evaluation and molecular modeling of 5-hydroxyisoquinolinium salt series; the effect of the hydroxyl moiety

Popis výsledku v původním jazyce

In the present paper, we describe the synthesis of a new group of 5-hydroxyisoquinolinium salts with different lengths of alkyl side-chain (C-10-C-18), and their chromatographic analysis and biological assay for in vitro activity against bacterial and fungal strains. We compare the lipophilicity and efficacy of hydroxylated isoquinolinium salts with the previously published (non-hydroxylated) isoquinolinium salts from the point of view of antibacterial and antifungal versatility and cytotoxic safety. Compound 11 (C-18) had to be excluded from the testing due to its low solubility. Compounds 9 and 10 (C-14, C-16) showed only moderate efficacy against G+ bacteria, notably with excellent potency against Staphyloccocus aureus, but no effect against G- bacteria. In contrast, non-hydroxylated isoquinolinium salts showed excellent antimicrobial efficacy within the whole series, particularly 14 (C-14) against G+ strains and 15 (C-16) against fungi. The electronic properties and desolvation energies of 5-hydroxyisoquinolinium and isoquinolinium salts were studied by quantum-chemistry calculations employing B3LYP/6-311++G(d,p) method and an implicit water-solvent simulation model (SCRF). Despite the positive mesomeric effect of the hydroxyl moiety reducing the electron density of the quaternary nitrogen, it is probably the higher lipophilicity and lower desolvation energy of isoquinolinium salts, which is responsible for enhanced antimicrobial versatility and efficacy. (c) 2016 Elsevier Ltd. All rights reserved.

Název v anglickém jazyce

Synthesis, antimicrobial evaluation and molecular modeling of 5-hydroxyisoquinolinium salt series; the effect of the hydroxyl moiety

Popis výsledku anglicky

In the present paper, we describe the synthesis of a new group of 5-hydroxyisoquinolinium salts with different lengths of alkyl side-chain (C-10-C-18), and their chromatographic analysis and biological assay for in vitro activity against bacterial and fungal strains. We compare the lipophilicity and efficacy of hydroxylated isoquinolinium salts with the previously published (non-hydroxylated) isoquinolinium salts from the point of view of antibacterial and antifungal versatility and cytotoxic safety. Compound 11 (C-18) had to be excluded from the testing due to its low solubility. Compounds 9 and 10 (C-14, C-16) showed only moderate efficacy against G+ bacteria, notably with excellent potency against Staphyloccocus aureus, but no effect against G- bacteria. In contrast, non-hydroxylated isoquinolinium salts showed excellent antimicrobial efficacy within the whole series, particularly 14 (C-14) against G+ strains and 15 (C-16) against fungi. The electronic properties and desolvation energies of 5-hydroxyisoquinolinium and isoquinolinium salts were studied by quantum-chemistry calculations employing B3LYP/6-311++G(d,p) method and an implicit water-solvent simulation model (SCRF). Despite the positive mesomeric effect of the hydroxyl moiety reducing the electron density of the quaternary nitrogen, it is probably the higher lipophilicity and lower desolvation energy of isoquinolinium salts, which is responsible for enhanced antimicrobial versatility and efficacy. (c) 2016 Elsevier Ltd. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Synthesis, antimicrobial evaluation and molecular modeling of 5-hydroxyisoquinolinium salt series; the effect of the hydroxyl moiety

ISSN

0968-0896

e-ISSN

1464-3391

Svazek periodika

24

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

841-848

Kód UT WoS článku

000368898500035

EID výsledku v databázi Scopus

2-s2.0-84956637018