A mononuclear N,N,N,O donor schiff base Cu(II) complex inhibits bacterial biofilm formation and promotes apoptosis and cell cycle arrest in prostate cancer cells.

In this work, we report a distorted square pyramidal mononuclear copper(II) complex [Cu(L)(NCS)] (1) which was obtained by the reaction of the aqueous solution of ammonium thiocyanate to a methanolic solution of copper nitrate trihydrate and corresponding Schiff-base ligands. Schiff bases, HL (C12H19N3O) act as a tetradentate Schiff base, derived from 1:1 condensation of o-hydroxyacetophenone and diethylenetriamine. The synthesized complex has been successfully characterized based on elemental analysis and Infrared (IR) spectroscopy. The structure of complex 1 was confirmed by single-crystal X-ray diffraction study. In our study, we investigated synthesis, structural characterization, antimicrobial, anti-biofilm, and anti-cancer activity, and plausible mechanism of action of a novel mononuclear copper(II) schiff base complex. Increasing microbial resistance to several commercially available or traditional antimicrobial compounds has become a major global health concern at present time. The mononuclear copper(II) complex exhibited potential antibacterial activity against two strains of the gram-negative pathogen Pseudomonas aeruginosa. The copper compound dependent damage of bacterial cell membrane and inhibition of bacterial biofilm formation were also identified. Moreover, complex 1 inhibited prostate cancer cell growth, and migration by inducing apoptosis and arresting the cell cycle at the G2/M phase. Based on the results, we are suggesting our novel mononuclear copper(II) compound as a potential candidate for the development of new antibacterial and anti-cancer drugs.

Development of Copper Nanoparticle Conjugated Chitosan Microparticle as a Stable Source of 2nm Copper Nanoparticle Effective against Methicillin- resistant Staphylococcus aureus.

BACKGROUND: Copper nanoparticle (CuNP) has well-established antimicrobial activity. Instability in an aqueous medium due to aggregation into larger particles, conversion into metal ions, and oxidation into metal oxides are the major limitations of its practical use against bacterial infections. OBJECTIVE: Development of CuNP Conjugated Chitosan Microparticles as a reservoir that will release CuNP effective against notorious bacteria like Methicillin-resistant Staphylococcus aureus. METHODS: CuNP conjugated chitosan microparticles (CNCCM) were synthesized using a simple twostep process. In the first step, a solution of chitosan in 2% (w/v) ascorbic acid was added dropwise in copper sulphate solution to prepare Cu ion conjugated chitosan beads. In the second step, these beads were soaked in sodium hydroxide solution to get the CNCCM. The dried CNCCM were characterized thoroughly for surface conjugation of CuNP, and the release of CuNP in a suitable medium. The physicochemical properties of release CuNP were further verified with the in silico modelled CuNP. The Antimicrobial and antibiofilm activities of released CuNp were evaluated against methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: 2% (w/v) ascorbic acid solution (pH 3.5) was the optimum medium for the release of ~2 nm CuNP from CNCCM. The CuNP had an optical band gap of ~ 2 eV. It inhibited the cell wall synthesis of MRSA. The minimum inhibitory concentration was 200 nM. At 100 nM dose, the CuNP caused ~73% reduction in biofilm development after 24 h of growth. The cytotoxic effect of CuNP on the human cell line (HEK 293) was significantly less than that on MRSA. The 48 h IC50 value against HEK 293 was 3.45-fold higher than the MIC value against MRSA after 24 h treatment. CONCLUSION: CuNP Conjugated Chitosan Microparticle has been developed. It works as a stable reservoir of ~2 nm CuNP. The CuNP is released in an aqueous medium containing 2% (w/v) ascorbic acid (pH 3.5). The released CuNP has a bacteriostatic effect against MRSA at a concentration safe for human cells.