Study of the Anticancer Properties of Tin(IV) Carboxylate Complexes on a Panel of Human Tumor Cell Lines

Carboxylic Acids Molecular Conformation Antineoplastic Agents Crystallography, X-Ray 01 natural sciences 0104 chemical sciences Coordination Complexes Drug Resistance, Neoplasm Tin Cell Line, Tumor Humans ATP Binding Cassette Transporter, Subfamily B, Member 1 Drug Screening Assays, Antitumor Cell Proliferation
DOI: 10.1002/cmdc.201100432 Publication Date: 2011-12-13T13:28:59Z
ABSTRACT
AbstractA 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.
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