| Affiliation: | 1. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoi St., 22, Ekaterinburg, 620990 Russia;2. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoi St., 22, Ekaterinburg, 620990 Russia
Ural Federal University named after the First President of Russia B.N. Yeltsin, Mira St., 19, Ekaterinburg, 620002 Russia;3. Ural Research Institute for Dermatology, Venereology and Immunopathology, Shcherbakova St., 8, Ekaterinburg, 620076 Russia;4. Ufa Institute of Chemistry of, Russian Academy of Science, Octyabrya St., 71, Ufa, 450078 Russia;5. Ural Federal University named after the First President of Russia B.N. Yeltsin, Mira St., 19, Ekaterinburg, 620002 Russia |
| 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. |
