1. Synergy of experimental and computational chemistry: structure and biological activity of Zn(II) hydrazone complexes.
- Author
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Savić M, Pevec A, Stevanović N, Novaković I, Matić IZ, Petrović N, Stanojković T, Milčić K, Zlatar M, Turel I, Čobeljić B, Milčić M, and Gruden M
- Subjects
- Humans, Cell Line, Tumor, Molecular Structure, Molecular Docking Simulation, Drug Screening Assays, Antitumor, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Models, Molecular, Fungi drug effects, Structure-Activity Relationship, Hydrazones chemistry, Hydrazones pharmacology, Hydrazones chemical synthesis, Zinc chemistry, Zinc pharmacology, Coordination Complexes pharmacology, Coordination Complexes chemistry, Coordination Complexes chemical synthesis, Density Functional Theory, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Antifungal Agents pharmacology, Antifungal Agents chemistry, Antifungal Agents chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Microbial Sensitivity Tests
- Abstract
In this paper, three different Zn(II) complexes with ( E )-2-(2-(1-(6-bromopyridin-2-yl)ethylidene)hydrazinyl)- N , N , N -trimethyl-2-oxoethan-1-aminium chloride (HLCl) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR and NMR spectroscopy. All complexes are mononuclear, with the ligand (L) coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Complex 1 forms an octahedral geometry with the composition [ZnL
2 ](BF4 )2 , while complexes 2 [ZnL(NCO)2 ] and 3 [ZnL(N3 )2 ] form penta-coordinated geometry. Density functional theory (DFT) calculations were performed to enhance our understanding of the structures of the synthesized complexes and the cytotoxic activity of the complexes was tested against five human cancer cell lines (HeLa, A549, MDA-MB-231, K562, LS 174T) and normal human fibroblasts MRC-5. Additionally, antibacterial and antifungal activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two fungal strains, and a yeast strain. It is noteworthy that all three complexes show selective antifungal activity comparable to that of amphotericin B. Molecular docking analysis predicted that geranylgeranyl pyrophosphate synthase, an enzyme essential for sterol biosynthesis, is the most likely target for inhibition by the tested complexes.- Published
- 2024
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