Schiff base Sn(IV) complexes as cytotoxic agents: Synthesis, structure, isosteric and bioisosteric replacement

Abstract

The preparation and characterization of two series of organotin(IV) complexes are reported, each series differing in the nature of the substituent bonded to the tin atom (cyclohexyl or bis(trimethyl)silylmethyl). The isosteric and bioisosteric approach was used as the strategy of molecular design. The ligand was 5-hydroxymethyl-4-[(2-hydroxyphenyl)iminomethyl]-2-methylpyridin-3-ol substituted at position 4 by methyl, halogeno (F, Cl), methoxy, nitro and tert-butyl; the synthesis of the organotin(IV) complexes was performed by a multi-component strategy in reasonable to high yields depending on the nature of the ligand. All new complexes were fully characterized by IR, MS, X-ray determinations and NMR (1H, 13C, 119Sn). Crystallographic data of complexes showed the geometries adopted around the metal tin center varied between square pyramidal in 2c and a trigonal bipyramidal in 3b-3d with the alkyl groups in the trigonal plane and the two oxygen atoms in the equatorial plane. Additionally, the in vitro cytotoxicity tests of the complexes towards six types of human cancerous cell lines U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (human colorectal), MCF-7 (human breast), MDA-MB-231(human breast) and SKLU-1 (non-small cell lung) showed the superior activity of the organotin complexes compared to the corresponding cisplatin used as positive control. The complexes containing fluorine exhibited excellent IC50 data indicating that both the bioisosteric replacement and the cyclohexyl ring bonded to the tin atom increased the potency of the cytotoxic activity towards the cancer cell lines tested.