Synthesis, antimicrobial evaluation and molecular modeling of 5-hydroxyisoquinolinium salt series; the effect of the hydroxyl moiety
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26774252
DOI
10.1016/j.bmc.2016.01.006
PII: S0968-0896(16)30005-0
Knihovny.cz E-zdroje
- Klíčová slova
- 5-Hydroxyisoquinolinium salts, Antimicrobial activity, Isoquinolinium salts, Lipophilicity, Synthesis,
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- antifungální látky chemická syntéza farmakologie MeSH
- gramnegativní bakterie účinky léků růst a vývoj MeSH
- grampozitivní bakterie účinky léků růst a vývoj MeSH
- houby účinky léků růst a vývoj MeSH
- isochinoliny chemická syntéza farmakologie MeSH
- kvantová teorie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární modely MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- antifungální látky MeSH
- isochinoliny MeSH
In the present paper, we describe the synthesis of a new group of 5-hydroxyisoquinolinium salts with different lengths of alkyl side-chain (C10-C18), 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 (C18) had to be excluded from the testing due to its low solubility. Compounds 9 and 10 (C14, C16) 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 (C14) against G+ strains and 15 (C16) 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.
Citace poskytuje Crossref.org
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