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.

Metal Complexes as Promising Agents for Biomedical Applications.

BACKGROUND: In this review article, a brief overview of novel metallotherapeutic agents (with an emphasis on the complexes of essential biometals) promising for medical application is presented. We have also focused on the recent work carried out by our research team, specifically the development of redox-active antimicrobial complexes of sterically hindered diphenols with some essential biometals (copper, zinc, nickel). RESULTS: The complexes of essential metals (manganese, iron, cobalt, nickel, copper, zinc) described in the review show diverse in vitro biological activities, ranging from antimicrobial and antiinflammatory to antiproliferative and enzyme inhibitory. It is necessary to emphasize that the type of organic ligands in these metal complexes seems to be responsible for their pharmacological activities. In the last decades, there has been a significant interest in synthesis and biological evaluation of metal complexes with redox-active ligands. A substantial step in the development of these redox-active agents is the study of their physicochemical and biological properties, including investigations in vitro of model enzyme systems, which can provide evidence on a plausible mechanism underlying the pharmacological activity. When considering the peculiarities of the pharmacological activity of the sterically hindered diphenol derivatives and their nickel(II), copper(II) and zinc(II) complexes synthesized, we took into account the following: (i) all these compounds are potential antioxidants and (ii) their antimicrobial activity possibly results from their ability to affect the electron-transport chain. CONCLUSION: We obtained novel data demonstrating that the level of antibacterial and antifungal activity in the series of the above-mentioned metal-based antimicrobials depends not only on the nature of the phenolic ligands and complexing metal ions, but also on the lipophilicity and reducing ability of the ligands and metal complexes, specifically regarding the potential biotargets of their antimicrobial action - ferricytochrome c and the superoxide anion radical. The combination of antibacterial, antifungal and antioxidant activity allows one to consider these compounds as promising substances for developing therapeutic agents with a broad spectrum of activities.

Synthesis, characterization, antifungal and anti-HIV activities of metal(II) complexes of 4,6-di-tert-butyl-3-[(2-hydroxyethyl)thio]benzene-1,2-diol.

Co(II) and Ni(II) complexes with 4,6-di-tert-butyl-3-[(2-hydroxyethyl)thio]benzene-1,2-diol (L) have been synthesized and characterized by means of elemental analysis, TG/DTA, FT-IR, ESR, UV-vis, XRD, magnetic susceptibility, cyclic voltammetry and conductance measurements. According to the data obtained the organic compound acts as a bidentate O,S-coordinated ligand and yields Co(II) and Ni(II) complexes of the stoichiometry ML(2) which is characterized by square planar geometry. Antifungal and anti-HIV activities of the ligand and its metal(II) complexes were found to decrease in the sequence CuL(2)>CoL(2) ~ NiL(2)>HL, along with their reducing ability (determined electrochemically).

Synthesis and biological evaluation of copper (II) complexes of sterically hindered o-aminophenol derivatives as antimicrobial agents.

Cu(II) complexes with 4,6-di(tert-butyl)-2-aminophenol (I) and 2-anilino-4,6-di(tert-butyl)phenol (II) have been synthesized and characterized by means of elemental analysis, TG/DTA, FT-IR, UV-vis, ESR, and conductance measurements. The compounds I and II can coordinate in their singly deprotonated forms and behave as bidentate O,N-coordinated ligands; their CuL(2) complexes are characterized by CuN(2)O(2) coordination modes and square planar geometry. In vitro antimicrobial screening against Gram-positive and Gram-negative bacteria, yeasts, and moulds indicated that the compound I and its Cu(II) complex were more active than Questiomycin B, the compound II, and its Cu(II) complex.