Vanadium() complexes derived from triphenylphosphonium and hydrazides: cytotoxicity evaluation and interaction with biomolecules

• Published in: Dalton transactions : an international journal of inorganic chemistry 2024-05, Vol.53 (19), p.8315-8327
• Main Authors: Martins, Francisco Mainardi, Iglesias, Bernardo Almeida, Chaves, Otávio Augusto, Gutknecht da Silva, Jean Lucas, Leal, Daniela Bitencourt Rosa, Back, Davi Fernando
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biomolecules; Cell Line, Tumor; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Coordination compounds; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - metabolism; Drug Screening Assays, Antitumor; Grooves; Humans; Hydrazides; Hydrazines - chemistry; Hydrazines - pharmacology; Hydrazones; Ligands; Molecular docking; Molecular Docking Simulation; Molecular Structure; NMR; Nuclear magnetic resonance; Organophosphorus Compounds - chemistry; Organophosphorus Compounds - pharmacology; Pharmacology; Proteins; Serum albumin; Serum Albumin, Human - chemistry; Serum Albumin, Human - metabolism; Single crystals; Structural stability; Toxicity; Vanadium; Vanadium - chemistry; Vanadium - pharmacology
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/d4dt00464g

The development of coordination compounds with antineoplastic therapeutic properties is currently focused on non-covalent interactions with deoxyribonucleic acid (DNA). Additionally, the interaction profiles of these compounds with globular plasma proteins, particularly serum albumin, warrant thorough evaluation. In this study, we report on the interactions between biomolecules and complexes featuring hydrazone-type imine ligands coordinated with vanadium. The potential to enhance the therapeutic efficiency of these compounds through mitochondrial targeting is explored. This targeting is facilitated by the derivatization of ligands with triphenylphosphonium groups. Thus, this work presents the synthesis, characterization, interactions, and cytotoxicity of dioxidovanadium( v ) complexes ( C1-C5 ) with a triphenylphosphonium moiety. These V V -species are coordinated to hydrazone-type iminic ligands derived from (3-formyl-4-hydroxybenzyl)triphenylphosphonium chloride ( [AH]Cl ) and aromatic hydrazides ( [H 2 L1]Cl-[H 2 L5]Cl ). The structures of the five complexes were elucidated through single-crystal X-ray diffraction and vibrational spectroscopies, confirming the presence of dioxidovanadium( v ) species in various geometries with degrees of distortion ( τ = 0.03-0.50) and highlighting their zwitterionic characteristics. The molecular structural stability of C1-C5 in solution was ascertained using 1 H, 19 F, 31 P, and 51 V-nuclear magnetic resonance. Moreover, their interactions with biomolecules were evaluated using diverse spectroscopic methodologies and molecular docking, indicating moderate interactions ( K b 10 4 M −1 ) with calf thymus DNA in the minor groove and with human serum albumin, predominantly in the superficial IB subdomain. Lastly, the cytotoxic potentials of these complexes were assessed in keratinocytes of the HaCaT lineage, revealing that C1-C5 induce a reduction in metabolic activity and cell viability through apoptotic pathways. This work presents the synthesis, characterization, interactions, and cytotoxicity of dioxidovanadium( v ) complexes ( C1-C5 ) with a triphenylphosphonium moiety.