Promising Antifungal and Antibacterial Agents Based on 5‐Aryl‐2,2′‐bipyridines and Their Heteroligand Salicylate Metal Complexes: Synthesis, Bioevaluation, Molecular Docking

Abstract

A series of new 5‐aryl‐2,2′‐bipyridines and their (polyfluoro)salicylate complexes of Cu(II), Co(II) and Mn(II) were synthesized. Their antimicrobial activity was evaluated in vitro against six strains of Trichophytons, E. floccosum, M. canis, C. ablicans and Gram‐negative bacteria N. gonorrhoeae. Among azo‐ligands, Ph‐bipy and Tol‐bipy showed promising antifungal activity (minimum inhibitory concentration (MIC)<0.8–27 μM). Their antifungal action was found can be realized via binding Fe(III) ions. Tol‐bipy suppressed growth of Gram‐positive bacteria S. aureus, S. aureus MRSA and their monospecies biofilms (MIC 6–16 μM). Using molecular docking, the anti‐staphylococcal action mechanism based on the inhibition of S. aureus DNA gyrase GyrB was proposed for the lead compounds. Among metal complexes, Cu(II) and Mn(II) complexes based on tetrafluorosalicylic acid and Tol‐bipy or Ph‐bipy had the high antifungal activity (MIC<0.24–32 μM). Mn(SalF4−2H)2(Tol‐bipy)2] suppressed the growth of seven Candida strains at MIC 12–24 μM. [Cu(Sal−2H)(Ph‐bipy)] and [Cu(SalF3−2H)(Ph‐bipy)2] showed the promising anti‐gonorrhoeae activity (MIC 4.2–5.2 μM). (Cu(SalFn−2H)(Tol‐bipy)2], [Cu(SalF4−2H)(Ph‐bipy)2] and [Cu(SalF3−2H)(Ph‐bipy)2]) were found active against the bacteria of S. aureus, S. aureus MRSA and their biofilms (MIC 2.4–41.4 μM). The most active compounds were tested for toxicity in vitro against human embryonic kidney (HEK‐293) cells and in vivo experiments with CD‐1 mice.

Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding

“…Whereas the inactive compounds did not show an affinity for the enzymes, our docking protocol identified two possible major targets for some molecules of this class of compounds, namely lipoteichoic acid flippase (LtaA) and lipoprotein signal peptidase II (LspA). To our knowledge, our study is the first reported attempt to computationally identify MRSA biological targets of antibiotic rhenium complexes [93][94][95][96][97]. Experimental data are required in the future to confirm the in silico results, but our data are in line with the limited mechanistic studies that have previously been published on microbicidal rhenium species.…”