Tin(IV) compounds of tridentate thiosemicarbazone Schiff bases: Synthesis, characterization, in-silico analysis and in vitro cytotoxicity.

Thiosemicarbazone Schiff bases 1 and 4 are useful lead candidates for future organic drug design development to treat cancers. Diphenyltin(IV) compounds 5, 8, 11 and 14 exhibited excellent cytotoxic activity against all the cancer cell lines tested. • Thiosemicarbazone Schiff bases 1 & 4 are useful lead candidates for anticancer drug development. • Diphenyltin(IV) compounds with trigonal bipyramidal geometry had excellent cytotoxicity. • Compounds 5, 8, 11 & 14 had the highest cytotoxicity against ten cancer cell lines tested. • Compounds 5, 8, 11 & 14 had low cytotoxicity against normal breast cancer cells MCF-10A. Twelve tin(IV) compounds (5 – 16) derived from four tridentate thiosemicarbazone Schiff bases of 4-methyl-3-thiosemicarbazide with 2-hydroxy-3-methoxybenzaldehyde (1, 2) and 4-phenyl-3-thiosemicarbazide with 2,3-dihydroxybenzaldehyde (3, 4) of the general formulae [R 2 Sn(L n)] and [Sn(L n) 2 ] (where R = Ph or Me; L n = 1 , 2 , 3 and 4) were synthesized and characterized by elemental analysis, IR, UV–vis, mass spectrometry and multinuclear NMR (1H, 13C and 119Sn) spectroscopy. X-ray crystallographic data was obtained for 11′ , a 2:1 co-crystal between Ph 2 Sn(L2) (11) and 3-methoxysalicylaldehyde azine, and Me 2 Sn(L2) (12) where L2H 2 is 2-(2-hydroxy-3-methoxybenzylidene)- N -phenylhydrazinecarbothioamide. The analysis revealed distinct coordination geometries for 11 and 12 approaching trigonal–bipyramidal. In the crystal of 11′ , supramolecular dimers arising from amine N H...S(thiolate) hydrogen bonding and {...HNCS} 2 synthons are evident; π(chelate ring)...π(oxidobenzylidene) stacking is also apparent. In the crystal of 12 , supramolecular, helical chains are generated by a combination of amine N H...O(phenoxide) hydrogen bonding and Sn...S secondary bonding. The cytotoxic activity of the compounds against a panel of ten cancer cell lines, [HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast), A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas), and one normal cell line, MCF-10A (normal breast)] were investigated. The thiosemicarbazone Schiff bases 1 and 4 as well as the diphenyltin(IV) compounds showed a strong ability to inhibit the growth of cancer cells, with particular selectivity against HT29, MCF-7, A2780, A431, BE2-C, SJ-G2 and MIA cell lines. The structure–activity relationship of all these compounds were studied by evaluating the effect of alkyl and aryl groups attached on the thiosemicarbazone backbone, the methoxy/hydroxyl groups present at the meta -position of the phenyl ring and alkyl or aryl groups bound to the tin center. [ABSTRACT FROM AUTHOR]