New dibutyltin(IV) ladders: Syntheses, structures and, optimization and evaluation of cytotoxic potential employing A375 (melanoma) and HCT116 (colon carcinoma) cell lines in vitro.

Abstract

Synthesis and spectroscopic properties of seven new dibutyltin(IV) compounds of 2-{(E)-4-hydroxy-3-[(E)-4-(aryl)iminomethyl]phenyldiazenyl}benzoic acids (LnHH'; n=2-8) with general formula {[Bu2Sn(LnH)]2O}2 (1-7) are reported. The compounds were characterized by elemental analysis and by UV-Visible, fluorescence, IR, 1H, 13C and 119Sn NMR spectroscopies. Solid state structures of dibutyltin(IV) compounds 1-3, 6 and 7 were accomplished from single crystal X-ray crystallography which reveal the common ladder-type structure with two endo- and two exo-Sn atoms. The redox properties of LnHH' (n=2-4, 7 and 8) and their diorganotin(IV) compounds 1-3, 6 and 7 were also investigated by cyclic voltammetry. In general, the dibutyltin(IV) derivatives exhibited significant in vitro cytotoxic potency towards A375 (melanoma) and HCT116 (colon carcinoma) cell lines as determined by several experiments, like Live and Dead assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), cleavage of caspases and PARP (poly(ADP-ribose)polymerase), and DNA fragmentation. Dibutyltin(IV) compounds increase cell death without cytolysis and decreases membrane fluidity, without interfering with p53. Among the dibutyltin(IV) compounds, compound 6 was found to be the most potent, with an IC50 value of 78nM. A mechanism of action for tumor cell death is proposed.

• Authors: Tushar S Basu Baul, Dhrubajyoti Dutta, Andrew Duthie, Nikhil Guchhait, Bruno G M Rocha, M Fátima C Guedes da Silva, Raveendra B Mokhamatam, Nune Raviprakash, Sunil K Manna
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 166 Pg. 34-48 (01 2017) ISSN: 1873-3344 [Electronic] United States
• PMID: 27815980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cytotoxins
• Organotin Compounds
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Membrane (metabolism, pathology)
• Cell Survival (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Crystallography, X-Ray
• Cytotoxins (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Magnetic Resonance Spectroscopy
• Melanoma (drug therapy, metabolism, pathology)
• Membrane Fluidity (drug effects)
• Molecular Structure
• Organotin Compounds (chemical synthesis, chemistry, pharmacology)
• Tumor Suppressor Protein p53 (metabolism)