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.