Radman Kastelic, Andreja; Odžak, Renata; Pezdirc, Iskra; Sović, Karlo; Hrenar, Tomica; Čipak Gašparović, Ana; Skočibušić, Mirjana; Primožič, Ines
(2019)
New and potent quinuclidine based antimicrobial agents.
Molecules, 24
(14).
pp. 2675-2692.
ISSN 1420-3049
Abstract
Developing new antibiotics is currently very important since antibiotic resistance is one of the biggest problems of global health today. In the search for a new class of potential antimicrobial agents, ten new compounds were designed and synthesized based on quinuclidinium heterocyclic core and oxime functional group. The antimicrobial activity was assessed against a panel of representative Gram-positive and Gram-negative bacteria. All compounds demonstrated potent activity against the tested microorganisms, with MIC values ranging from 0.25 to 256.00 μg/mL. Among the tested compounds, two quaternary compounds, para-N-chlorobenzyl and meta-N-bromobenzyl quinuclidinium oximes, displayed the most potent and broad-spectrum activity against both Gram-positive and Gram-negative bacterial strains (MIC values from 0.25 to 4.00 μg/mL), with the lowest value for the important multidrug resistant Gram-negative pathogen Pseudomonas aeruginosa. In the case of Klebsiella pneumoniae activity of those compounds are 256-fold and 16-fold better than gentamicin, respectively. MTT assay showed that compounds are nontoxic for human cell lines. Multi-way analysis was used to separately reduce dimensionality of quantum chemical data and biological activity data to obtain regression model and required parameters for the enhancement of biological activity.
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