Please use this identifier to cite or link to this item: http://repositorio.ufla.br/jspui/handle/1/36721
metadata.artigo.dc.title: Towards understanding the mechanism of action of antibacterial N-alkyl-3-hydroxypyridinium salts: Biological activities, molecular modeling and QSAR studies
metadata.artigo.dc.creator: Dolezal, Rafael
Soukup, Ondrej
Malinak, David
Savedra, Ranylson M. L.
Marek, Jan
Dolezalova, Marie
Pasdiorova, Marketa
Salajkova, Sarka
Korabecny, Jan
Honegr, Jan
Ramalho, Teodorico C.
Kuca, Kamil
metadata.artigo.dc.subject: Quaternary ammoniums salts
Antimicrobials
Surfactants
Molecular modeling
Molecular dynamics
QSAR
Sais de amônio quaternário
Antimicrobianos
Surfactantes
Modelagem molecular
Dinâmica molecular
metadata.artigo.dc.publisher: Elsevier
metadata.artigo.dc.date.issued: 4-Oct-2016
metadata.artigo.dc.identifier.citation: DOLEZAL, R. et al. Towards understanding the mechanism of action of antibacterial N-alkyl-3-hydroxypyridinium salts: Biological activities, molecular modeling and QSAR studies. European Journal of Medicinal Chemistry, Paris, v. 121, p. 699-711, 4 Oct. 2016.
metadata.artigo.dc.description.abstract: In this study, we have carried out a combined experimental and computational investigation to elucidate several bred-in-the-bone ideas standing out in rational design of novel cationic surfactants as antibacterial agents. Five 3-hydroxypyridinium salts differing in the length of N-alkyl side chain have been synthesized, analyzed by high performance liquid chromatography, tested for in vitro activity against a panel of pathogenic bacterial and fungal strains, computationally modeled in water by a SCRF B3LYP/6-311++G(d,p) method, and evaluated by a systematic QSAR analysis. Given the results of this work, the hypothesis suggesting that higher positive charge of the quaternary nitrogen should increase antimicrobial efficacy can be rejected since 3-hydroxyl group does increase the positive charge on the nitrogen but, simultaneously, it significantly derogates the antimicrobial activity by lowering the lipophilicity and by escalating the desolvation energy of the compounds in comparison with non-hydroxylated analogues. Herein, the majority of the prepared 3-hydroxylated substances showed notably lower potency than the parent pyridinium structures, although compound 8 with C12 alkyl chain proved a distinctly better antimicrobial activity in submicromolar range. Focusing on this anomaly, we have made an effort to reveal the reason of the observed activity through a molecular dynamics simulation of the interaction between the bacterial membrane and compound 8 in GROMACS software.
metadata.artigo.dc.identifier.uri: https://www.sciencedirect.com/science/article/pii/S0223523416304561#!
http://repositorio.ufla.br/jspui/handle/1/36721
metadata.artigo.dc.language: en_US
Appears in Collections:DQI - Artigos publicados em periódicos

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