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

• DOI: 10.1002/cmdc.201100432
• Publication Date: 2011-12-13T13:28:59Z
• Authors: Lourdes Rocamora‐...; Estefanía Carrasc...; Jesús Ceballos‐To...; Sanjiv Prashar; Goran N. Kaluđerović; José A. Ferragut; Santiago Gómez‐Ruiz
• Keywords: 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

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.