ABSTRACT
Antimicrobial resistance has emerged as a covert global health crisis, posing a significant threat to humanity. If left unaddressed, it is poised to become the foremost cause of mortality worldwide. Among the multitude of resistant bacterial pathogens, Pseudomonas aeruginosa, a Gram-negative, facultative bacterium, has been responsible for mild to deadly infections. It is now enlisted as a global critical priority pathogen by WHO. Urgent measures are required to combat this formidable pathogen, necessitating the development of novel anti-pseudomonal drugs. To confront this pressing issue, we conducted an extensive screening of 3561 compounds from the ChemDiv library, resulting in the discovery of potent anti-pseudomonal quinazoline derivatives. Among the identified compounds, IDD-8E has emerged as a lead molecule, exhibiting exceptional efficacy against P. aeruginosa while displaying no cytotoxicity. Moreover, IDD-8E demonstrated significant pseudomonal killing, disruption of pseudomonal biofilm and other anti-bacterial properties comparable to a well-known antibiotic rifampicin. Additionally, IDD-8E's synergy with different antibiotics further strengthens its potential as a powerful anti-pseudomonal agent. IDD-8E also exhibited significant antimicrobial efficacy against other ESKAPE pathogens. Moreover, we elucidated the Structure-Activity-Relationship (SAR) of IDD-8E targeting the essential WaaP protein in P. aeruginosa. Altogether, our findings emphasize the promise of IDD-8E as a clinical candidate for novel anti-pseudomonal drugs, offering hope in the battle against antibiotic resistance and its devastating impact on global health.
Subject(s)
Anti-Bacterial Agents , Drug Synergism , Pseudomonas aeruginosa , Quinazolines , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Quinazolines/pharmacology , Quinazolines/chemistry , Structure-Activity RelationshipABSTRACT
In this paper, we study the degree of approximation of 2π-periodic functions of two variables, defined on [Formula: see text] and belonging to certain Lipschitz classes, by means of almost Euler summability of their Fourier series. The degree of approximation obtained in this way depends on the modulus of continuity associated with the functions. We also derive some corollaries from our theorems.
