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Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable apoptosis mediated by reactive oxygen species

Version 2 2024-06-04, 03:01
Version 1 2017-06-07, 20:21
journal contribution
posted on 2024-06-04, 03:01 authored by TS Basu Baul, D Dutta, Andrew DuthieAndrew Duthie, R Prasad, NK Rana, B Koch, ERT Tiekink
The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(L(n))] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where L(n)=L(1-3); isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L(4-6) are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR ((1)H, (13)C, (119)Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL(4)) and two representative molecules, Ph3Sn(L(2)) 2 and Ph3Sn(L(5)) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50 value of 1.19 and 1.44μM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50 value of 0.88μM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.

History

Journal

Journal of inorganic biochemistry

Volume

173

Pagination

79-92

Location

Amsterdam, The Netherlands

ISSN

0162-0134

eISSN

1873-3344

Language

eng

Publication classification

C Journal article, C1 Refereed article in a scholarly journal

Copyright notice

2017, Elsevier Inc

Publisher

Elsevier