Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

• Published in: Inorganic chemistry Vol. 60; no. 20; pp. 15291 - 15309
• Main Authors: Sahu, Gurunath, Banerjee, Atanu, Samanta, Rajib, Mohanty, Monalisa, Lima, Sudhir, Tiekink, Edward R. T, Dinda, Rupam
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.10.2021
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; DNA - chemistry; Drug Screening Assays, Antitumor; Humans; Hydrazones - chemistry; Hydrazones - pharmacology; Hydrophobic and Hydrophilic Interactions; Mice; Models, Molecular; Molecular Structure; NIH 3T3 Cells; Serum Albumin, Bovine - chemistry; Solubility; Vanadium Compounds - chemistry; Vanadium Compounds - pharmacology; Water - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.1c01899

Five new anionic aqueous dioxidovanadium­(V) complexes, [{VO2L1,2}­A­(H2O) n ]α (1–5), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)­hydrazide (H2L1) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)­hydrazide (H2L2) incorporating different alkali metals (A = Na+, K+, Cs+) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1–5 were determined by time-dependent NMR and UV–vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2–4 confirmed the presence of vanadium­(V) centers coordinated by two cis-oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1–5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC50 value of 5.42 ± 0.15 μM showed greater activity in comparison to cisplatin against the HT-29 cell line.