Cytotoxic activity of organotin compounds containing non-steroidal anti-inflammatory drugs

• Published in: Journal of organometallic chemistry Vol. 960; pp. 122191 - 122200
• Main Authors: Antonenko, T.A., Gracheva, Yu.A., Shpakovsky, D.B., Vorobyev, M.A., Tafeenko, V.A., Mazur, D.M., Milaeva, E.R.
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 15.02.2022; Elsevier
• Subjects: Apoptosis; Aspirin; Cancer cells; Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Cytotoxicity; Diclofenac; Organotin complexes; Physical Sciences; Science & Technology; Cytotoxicity; Aspirin; Organotin complexes; Cancer cells; Diclofenac; Apoptosis; INHIBITION; MECHANISM; COMPLEXES; DERIVATIVES
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2021.122191

•Seven organotin compounds based on diclofenac and aspirin (NSAIDs) were synthesized.•The molecular structures of three complexes were determined by XRD analysis.•Cytotoxicity on cancer cell lines depends on the coordination number of Sn, the nature of substituent at sn atom and its lipophilicity.•Triphenyltin derivative with diclofenac demonstrates the highest cytotoxicity and significantly induces apoptosis of HCT-116 cells. Two series of organotin (IV) complexes based on diclofenac L1Na and aspirin L2H of formulae Me3SnL1 (1); Ph3SnL1 (2); Bu2Sn(L1)2 (3); R2Sn(L1)2 (4, R = 3,5-di-tert-butyl-4-hydroxyphenyl); Me3SnL2 (5); Me3Sn(2-hydroxybenzoate) (6) and Me2Sn(L2)2 (7) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. It was found by X-ray diffraction analysis of compound 1 that carboxyl group of diclofenac binds two tin atoms each being in the trigonal bipyramid geometry and having coordination number 5. Compounds 6 and 7 were found to be monomers in the solid state with tetrahedron and octahedron geometry around Sn center, respectively. Cytotoxicity in vitro of compounds 1–7 and initial ligands was evaluated on human colon cancer (HCT-116), human breast cancer (MCF-7) and adenocarcinomic human alveolar basal epithelial (A-549) cells. The IC50 values varied in 0.17–200 µM range for compounds 1–4 and in 3.3–200 µM range for compounds 5–7 depending on the substituents at Sn center and ligand structure. It was found that compound 2 possesses the maximal cytotoxic activity and significantly induces apoptosis of HCT-116 cells. [Display omitted] Novel organotin complexes with NSAIDs were synthesized. The in vitro antitumor activity of the complexes against human cancer cells was studied. High cytotoxicity was demonstrated.