Synthesis, structural characterization and in vitro antiproliferative effects of novel organotin(iv) compounds with nicotinate and isonicotinate moieties on carcinoma cells

Abstract

In recent decades, organotin(IV) chemistry has seen a rapid growth owing to the biological, pharmaceutical and medicinal applications found for different compounds. The aim of this study was the evaluation of the antiproliferative activity of several organotin(IV) compounds for a better understanding of the structure–activity relationship (SAR). The synthesis and structural features of the new organotin(IV) species are also presented. Thus, the treatment of [2-{(CH₂O)₂CH}C₆H₄]Me₂SnCl (1) and [2-(OCH)C₆H₄]Me₂SnCl (2) with potassium salts of isonicotinic and nicotinic acids resulted in the isolation of [2-{(CH₂O)₂CH}C₆H₄]Me₂Sn[O(O)CC₅H₄N-4] (3), [2-{(CH₂O)₂CH}C₆H₄]Me₂Sn[O(O)CC₅H₄N-3] (4), [2-(OCH)C₆H₄]Me₂Sn[O(O)CC₅H₄N-4] (5) and [2-(OCH)C₆H₄]Me₂Sn[O(O)CC₅H₄N-3] (6), respectively, in high yields. The one pot reaction between compound 2, isonicotinic acid and sodium hydroxide allows the formation of [2-(EtOOC)C₆H₄]Me₂Sn[O(O)(CC₅H₄N-4)] (7) in a moderate yield. The novel compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry and IR spectroscopy. The molecular structures of compounds 3–5 and 7 were established via single crystal X-ray diffraction; in all cases a distorted trigonal bipyramidal coordination geometry was found around the metal center, as a result of the strong intramolecular O→Sn coordination. Compounds 1–6 were investigated for their in vitro antiproliferative activity towards the mouse colon carcinoma C26 cell line with the preliminary results showing a better activity than that of 5-fluorouracil.