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 the quinuclidinium heterocyclic core and the 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 the minimum inhibitory concentration (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 assays 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 a regression model and the required parameters for the enhancement of biological activity.
Highlights
Infectious diseases are the second leading cause of death worldwide and cause significant morbidity, having a profound effect on global health [1]
Various health organizations have spoken about the urgent need to develop new antibiotics, especially against drug-resistant gram-negative ESKAPE
The World Health Organization (WHO) has raised its utmost concern about the post-antibiotic era where common infections and minor injuries may result in significant morbidity
Summary
Infectious diseases are the second leading cause of death worldwide and cause significant morbidity, having a profound effect on global health [1]. Various health organizations have spoken about the urgent need to develop new antibiotics, especially against drug-resistant gram-negative ESKAPE bacilli. The World Health Organization (WHO) has raised its utmost concern about the post-antibiotic era where common infections and minor injuries may result in significant morbidity. Molecules 2019, 24, 2675 utmost concern about the post-antibiotic era where common infections and minor injuries may result in significant morbidity mortality [4]. An potential strategy to helpinvolves combat the and mortality [4]. An importantand potential strategy to important help combat the resistance problem the resistance problem involvesofthe discovery and development of new active agents capable of partly discovery and development new active agents capable of partly or completely suppressing bacterial or completely suppressing bacterial resistance mechanisms
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