Chemmedchem 2012-02-06

Study of the anticancer properties of tin(IV) carboxylate complexes on a panel of human tumor cell lines.

Lourdes Rocamora-Reverte, Estefanía Carrasco-García, Jesús Ceballos-Torres, Sanjiv Prashar, Goran N Kaluđerović, José A Ferragut, Santiago Gómez-Ruiz

Index: ChemMedChem 7(2) , 301-10, (2012)

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Abstract

A group of organotin(IV) complexes were prepared: [SnCy3 (DMNI)] (1), [SnCy3 (BZDO)] (2), [SnCy3 (DMFU)] (3), and [SnPh2 (BZDO)2 ] (4), for which DMNIH=2,6-dimethoxynicotinic acid, BZDOH=1,4-benzodioxane-6-carboxylic acid, and DMFUH=2,5-dimethyl-3-furoic acid. The cytotoxic activities of compounds 1-4 were tested against pancreatic carcinoma (PANC-1), erythroleukemia (K562), and two glioblastoma multiform (U87 and LN-229) human cell lines; they show very high antiproliferative activity, with IC50 values in the 150-700 nM range after incubation for 72 h. Distribution of cellular DNA upon treatment with 1-4 revealed that whereas compounds 1-3 induce apoptosis in most of the cell lines, compound 4 does not affect cell viability in any cell line tested, indicating a possible difference in cytotoxic mechanism. Studies with the daunomycin-resistant K562/R cell line expressing P-glycoprotein (Pgp) showed that compounds 1-4 are not substrates of this protein efflux pump, indicating that these compounds do not induce acquisition of multidrug resistance, which is associated with the overexpression of Pgp.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.