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LVO-Ethyl Maltol-Based Metallodrugs (L = Tridentate ONO Ligands): Hydrophobicity, Hydrolytic Stability, and Cytotoxicity via ROS-Mediated Apoptosis. | LitMetric

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Article Abstract

Four new oxidovanadium [VOL(ema)] complexes (-) have been synthesized using tridentate binegative ONO donor ligands HL [HL: ()--(2-hydroxybenzylidene)furan-2-carbohydrazide; HL: ()--(4-(diethylamino)-2-hydroxybenzylidene)thiophene-2-carbohydrazide; HL: ()-2-(4-(diethylamino)-2-hydroxybenzylideneamino)-4-methylphenol; HL: ()-2-(3-ethoxy-2-hydroxybenzylideneamino)-4-methylphenol] and ethyl maltol (Hema) as a bidentate uninegative coligand and characterized by CHNS analysis, IR, UV-vis, NMR, and HR-ESI-MS methods. The structures of , , and are confirmed by single-crystal X-ray analysis. The hydrophobicity and hydrolytic stability of the complexes are tested using NMR and HR-ESI-MS and correlated with their observed biological activities. It is observed that hydrolyzed into a penta-coordinated vanadium-hydroxyl species (VOL-OH) with the release of ethyl maltol, whereas - are found quite stable under the investigated time period. The biomolecular interaction of - with DNA and BSA was performed using absorbance, fluorescence, and circular dichroism techniques. The cytotoxicity activities of HL and - were tested against A549, HT-29, and NIH-3T3 cell lines. Among complexes, with an IC value of 4.4 ± 0.1 μM displayed maximum anticancer activity against the HT-29 cell line. Complexes induce cell cycle arrest at the G2/M phase and subsequently trigger dose-dependent cell apoptosis, which is obtained by the cell apoptosis analysis via flow cytometry and confocal microscopy assays. Being fluorescence active, - were observed to target the mitochondria and exhibit disruption of the mitochondrial membrane potential, which consequently causes overproduction of intracellular reactive oxygen species and induced cell apoptosis.

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http://dx.doi.org/10.1021/acs.inorgchem.3c00326DOI Listing

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