Sterically hindered phenolic derivatives: effect on the production of Pseudomonas aeruginosa virulence factors, high-throughput virtual screening and ADME properties prediction.

Inhibition of quorum sensing is considered to be an effective strategy of control and treatment of a wide range of acute and persistent infections. Pseudomonas aeruginosa is an opportunistic bacterium with a high adaptation potential that contributes to healthcare-associated infections. In the present study, the effects of the synthesized hybrid structures bearing sterically hindered phenolic and heterocyclic moieties in a single scaffold on the production of virulence factors by P. aeruginosa were determined. It has been shown that the obtained compounds significantly reduce both pyocyanin and alginate production and stimulate the biosynthesis of siderophores in vitro, which may be attributed to their iron-chelating properties. The results of docking-based inverse high-throughput virtual screening indicate that transcription regulator LasR and Cu-transporter OPRC could be potential molecular targets for these compounds. Investigation of the impact small molecules exert on the molecular mechanisms of the production of bacterial virulence factors may pave the way for the design and development of novel antibacterial agents.

Bismuth(III) Complexes with Schiff Bases: Synthesis, Characterization, Interaction with Biomolecules, Antioxidant and Antimicrobial Activity.

AIMS AND BACKGROUND: In contrast to antibiotics, metal complexes can realize more than one mechanism of biocidal action to fight multidrug-resistant bacterial strains (due essentially to the metal ions), involving targets like functional groups in the walls of microbial cells and various enzymes. Among the potential antimicrobials are Bi(III) complexes with diphenols. OBJECTIVE: The present work aimed at synthesizing and investigating novel Bi(III) complexes with Schiff bases as potential antimicrobial and antioxidant agents. METHODS: Bi(III) complexes were characterized by means of elemental analysis, FT-IR, UV-Vis, 1H NMR spectroscopy, XRD, cyclic voltammetry and conductivity measurements as well as biological methods. RESULTS: The complexes are characterized by the formula Bi(L)2Cl and pyramidal geometry of their coordination cores BiO2N2Cl, wherein the Bi(III) cation is coordinated by hydroxyl and azomethine moieties. The ligands coordinate in their monoanionic forms. The complexes are more lipophilic and more bioactive against the bacteria tested than the ligands. Both the ligands and their complexes exhibited the capability for the Fe(III)-Cyt c reduction and displayed comparable reducing rates. All the compounds are characterized by the DPPH and ABTS radical scavenging activity, and they are more active reductants than Trolox in the CUPRAC assay too. The peculiarities of the interaction of the complexes with BSA suggest that Cys-34 of BSA is not a major binding site for these complexes. According to molecular docking studies, the complexes bind to BSA via non-covalent interactions. CONCLUSION: Bi(III) complexation with Schiff bases plays an important role in their antimicrobial and antioxidant activities as well as in their interaction with BSA.