Promising Antifungal and Antibacterial Agents Based on 5-Aryl-2,2'-bipyridines and Their Heteroligand Salicylate Metal Complexes: Synthesis, Bioevaluation, Molecular Docking.
Yanina V BurgartEvgeny V ShchegolkovIrina ShchurDmitry KopchukNatalia GerasimovaSophia BorisevichNatalia EvstigneevaGrigory ZyryanovMaria SavchukMaria UlitkoNatalia ZilberbergNikolai KungurovVictor I SaloutinValery N CharushinOleg N ChupakhinPublished in: ChemMedChem (2021)
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.
Keyphrases
- molecular docking
- metal organic framework
- aqueous solution
- candida albicans
- staphylococcus aureus
- methicillin resistant staphylococcus aureus
- molecular dynamics simulations
- escherichia coli
- induced apoptosis
- metabolic syndrome
- oxidative stress
- single molecule
- cell proliferation
- quantum dots
- cystic fibrosis
- skeletal muscle
- room temperature
- cell free
- multidrug resistant
- binding protein