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

Abstract

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 general formulae of [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, UVvis, mass spectrometry and multinuclear NMR (1 H, 13 C and 119 Sn) spectroscopy. X-ray crystallographic data was obtained for 11′ , a 2:1 co-crystal between Ph 2 Sn(L 2) (11) and 3-methoxysalicylaldehyde azine, and Me 2 Sn(L 2) (12); L 2 H 2 is 2-(2-hydroxy-3-methoxybenzylidene)-Nphenylhydrazinecarbothioamide. The analysis revealed distinct coordination geometries with 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 at 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.

Di-n-butyl[N′-(3-methoxy-2-oxidobenzylidene)-N-phenylcarbamohydrazonothioato]tin(IV): crystal structure, Hirshfeld surface analysis and computational study

“…The improvement of cytotoxic activity was also suggested to be due to the presence of OH/NH groups, which enabled hydrogen bonding with DNA base pairs (Haque et al, 2015). As part of our on-going studies in the structural elucidation and cytotoxic activity of tin(IV) compounds containing thiosemicarbazones Schiff base (Yusof et al, 2020), herein are described the synthesis of the title dibutyltin(IV) derivative, (I), its single crystal X-ray diffraction analysis and a detailed study of supramolecular association by an analysis of the calculated Hirshfeld surfaces and computational chemistry.…”

“…R = R 0 = Me (II) and Ph (III) (Cambridge Structural Database refcodes MUWQED and MUWQAZ, respectively; Yusof et al, 2020) and R = n-Bu and R 0 = CH 2 SiMe 3 (IV; CUJHIB; Xie et al, 2020). It is noted that the R = R 0 = Ph derivative (III) co-crystallized with onehalf mole equivalent of 3-methoxysalicylaldehyde azine (Yusof et al, 2020). Also, two positions were modelled for the tin atom in (IV), with the major component having a site occupancy factor = 0.523 and is designated hereafter as (IVa).…”

“…The synthesis of the Schiff base precursor, [2-(2-hydroxy-3methoxybenzylidene)-N-phenylhydrazine carbothioamide] was according to the procedure described in the literature (Ðilović et al, 2008;Kalaivani et al, 2012) with some modifications (Yusof et al, 2020). 4-Phenylthiosemicarbazide (1.67 g, 10 mmol) was dissolved in methanol (40 ml) with stirring and heating (313 K) over a period of 30 min.…”

Synthesis, characterisation and biological activity of diorganotin compounds of (E)-N'-(5-nitro-2-hydroxybenzylidene)-3-hydroxy-2-naphthohydrazide

“…Any modification in any one or more of the aforementioned factors could dramatically influence the observed biological activity. As a result, there is considerable interest in organotin Schiff base derivatives, especially those with various combinations of N-, O-and S-donor ligands [29][30][31][32][33][34].…”

Synthesis, characterization, thermal degradation, docking, DFT calculation, and biological activity of dimethyltin(IV) complex with homopiperazine

“…It is known that organotin(IV) compounds have an important role in cancer chemotherapy. [ 21–23 ] Numerous diorganotin(IV) derivatives exhibited high in vivo cytotoxicity against P388 lymphocytic leukemia. [ 24–26 ]…”