1. Amine-substituted heterocyclic thioamide Cu(I) and Ag(I) complexes as effective anticancer and antibacterial agents targeting the periplasm of E. coli bacteria.
- Author
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Varna D, Geromichalos GD, Dalezis P, Hatzidimitriou AG, Psomas G, Zachariadis G, Psatha K, Aivaliotis M, Papi R, Trafalis D, and Angaridis PA
- Subjects
- Humans, Molecular Structure, Structure-Activity Relationship, Amines chemistry, Amines pharmacology, Amines chemical synthesis, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Cell Line, Tumor, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology, Heterocyclic Compounds chemical synthesis, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Escherichia coli drug effects, Copper chemistry, Copper pharmacology, Thioamides chemistry, Thioamides pharmacology, Thioamides chemical synthesis, Microbial Sensitivity Tests, Coordination Complexes pharmacology, Coordination Complexes chemistry, Coordination Complexes chemical synthesis, Silver chemistry, Silver pharmacology, Drug Screening Assays, Antitumor
- Abstract
Metal complexes showing dual activity against cancer and bacterial infections are currently the focus of significant interest for their potential in treating life-threatening diseases. Aiming to investigate the impact of ligand substituents on these bioactivity properties of Group 11 d
10 metal complexes, we herein present a series of mononuclear Cu(I) and Ag(I) complexes featuring the bis-NH2 -substituted heterocyclic thioamide dap2SH (=4,6-diaminopyrimidine-2-thione), namely [AgCl(dap2SH)(PPh3 )2 ] (1), [CuBr(dap2SH)(PPh3 )2 ] (2), [CuBr(dap2SH)(xantphos)] (3), [Ag(dap2S)(xantphos)] (4), and [Cu(dap2S)(xantphos)] (5) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). Complexes were characterized by means of different physicochemical methods (i.e., single crystal X-ray diffraction as well as FTIR, NMR, UV-Vis and fluorescence spectroscopy), and studied in-vitro for their antibacterial and anticancer activity against a variety of bacterial strains and cancer cell lines. Complexes 1-3 effectively inhibited both Gram (+) and Gram (-) bacterial growth, while cellular uptake studies for the most potent complex 1 against E. coli bacteria revealed the accumulation of Ag(I) ions in the periplasm of the bacteria. A high anti-proliferative effect was observed for 1 and 5 against A549, MCF7 and PC3 cancer cell lines, with 1 being capable of inducing apoptosis in A549 cells, as suggested by flow cytometry analysis. DNA interaction studies revealed the capacity of 1 to intercalate between base-pairs of CT DNA. All complexes had a moderate-to-high capacity to scavenge free radicals preventing oxidative stress. Molecular docking calculations, in combination with the experimentally obtained data, provided insights for potential mechanisms of the bioactivity of the complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)- Published
- 2024
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