Triphenyltin(IV) compounds bearing modulated azo-carboxylato ligands: Synthesis, structural characterization, in vitro cytotoxicity, BSA/DNA binding affinity, and in silico studies

• Published in: Journal of organometallic chemistry 2024-06, Vol.1013, p.123158, Article 123158
• Main Authors: Pantelić, Nebojša Đ., Dimić, Dušan, Saoud, Mohamad, Matović, Luka R., Stević, Snežana Jovanović, Kasalović, Marijana P., Dojčinović, Biljana, Zmejkovski, Bojana B., Banjac, Nebojša R., Kaluđerović, Goran N.
• Format: Article
• Language: English
• Subjects: Breast cancer; Cytotoxicity; DFT; DNA/BSA interactions; Flow cytometry; Triphenyltin(IV)
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2024.123158

•Three novel Ph3Sn(IV) azo-carboxylato compounds were synthesized and characterized.•((E)−4-((4-(dimethylamino)phenyl)diazenyl)benzoato)Ph3Sn(IV), 3, has highest activity.•3 kills all investigated tumor cells at lower nanomolar concentrations.•3 induced apoptosis in MCF-7 cells, inhibits cell division and boosts cellular nO.•Compounds interact with calf thymus DNA and bovine serum albumin. Three novel triphenyltin(IV) compounds with modulated azo-carboxylato ligands: triphenylstannyl (E)-4-((2-hydroxynaphthalen-1-yl)diazenyl)benzoate, 1, triphenylstannyl (E)-4-((4-hydroxyphenyl)diazenyl)benzoate, 2, and triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, 3, were synthesized and characterized by elemental analysis, FTIR and NMR (1H, 13C, 119Sn) spectroscopy. The structures and spectra of compounds were predicted by Density Functional Theory (DFT) methods at B3LYP-D3BJ/6–311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level of theory. Furthermore, the antitumor potential of ligand precursors, HL1–HL3, and appropriate organotin(IV) compounds 1–3 was evaluated across mouse melanoma B16F1, human breast adenocarcinoma MCF-7, human colorectal HT-29 and human prostate PC3 cell lines using MTT and CV assays. The organotin(IV) compounds exhibit enhanced cellular uptake and efficacy in reducing viable cell numbers when compared to free acids. Specifically, compound 3 demonstrates a notable impact at lower nanomolar concentrations on all tested cell lines. Moreover, 3 induces cell death in MCF-7 cells by inhibiting cell division and promoting the overproduction of cellular nitric oxide (NO), ultimately leading to caspase-independent apoptosis. Importantly, this process occurs without concurrent activation of autophagy or the generation of ROS/RNS species. The binding affinity of 1–3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy and molecular docking simulations, suggesting their capacity to interact with these biomolecules. Three novel triphenyltin(IV) compounds with azo-carboxylato ligands were synthesized and characterized. Notably 3, triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, showed significant antitumor potential across various cell lines, inducing caspase-independent apoptosis in MCF-7 cells. Compound 3 exhibited enhanced cellular uptake and interaction potential with biomolecules DNA and BSA, emphasizing its biomedical application potential. [Display omitted]