Amino acetate functionalized Schiff base organotin(IV) complexes as anticancer drugs: synthesis, structural characterization, and in vitro cytotoxicity studies.

Potassium 2-{[(2Z)-(3-hydroxy-1-methyl-2-butenylidene)]amino}-4-methyl-pentanoate (L(1)HK) and potassium 2-{[(E)-1-(2-hydroxyphenyl)alkylidene]amino}-4-methyl-pentanoates (L(2)HK-L(3)HK) underwent reactions with Ph(n)SnCl(4-n) (n = 2 and 3) to give the amino acetate functionalized Schiff base organotin(IV) complexes [Ph(3)SnLH](n)(1-3) and [Ph(2)SnL] (4), respectively. These complexes have been characterized by (1)H, (13)C, (119)Sn NMR, IR spectroscopic techniques in combination with elemental analyses. The crystal structures of 1 and 3 were determined. The crystal structures reveal that the complexes exist as polymeric chains in which the L-bridged Sn-atoms adopt a trans-R(3)SnO(2) trigonal bipyramidal configuration with the Ph groups in the equatorial positions and the axial locations occupied by a carboxylate oxygen atom from one carboxylate ligand and the alcoholic or phenolic oxygen atom of the next carboxylate ligand in the chain. The carboxylate ligands coordinate in the zwitterionic form with the alcoholic/phenolic proton moved to the nearby nitrogen atom. The solution structures were predicted by (119)Sn NMR spectroscopy. When these organotin(IV) complexes were tested against A498, EVSA-T, H226, IGROV, M19 MEL, MCF7 and WIDR human tumor cell lines, the average ID(50) values obtained were 55, 80 and 35 ng/ml for triphenyltin(IV) compounds 1-3, respectively. The most cytotoxic triphenyltin(IV) compound in the present report (3) with an average ID(50) value of around 35 ng/ml is found to be more cytotoxic for all the cell lines studied than doxorubicin, cisplatin, 5-fluorouracil and etoposide.

Cell proliferation inhibition and antitumor activity of novel alkyl series of diorganotin(IV) compounds.

Diorganotin(IV) compounds, R2SnCl2 are often tetrahedral, and structurally resemble the active platinum compounds, i.e. cisplatin, and consequently a large number of such complexes have been tested for antitumor activity. A structural correlation with biological activity for diorganotin(IV) complexes has shown that active species are associated with complexes having Sn-N bonds longer than 2.39 A which in turn determines the formation of a tin-DNA complex. In view of these, a series of diorganotin(IV) dichloride complexes of N-(2-pyridylmethylene)arylamine (nitrogen-chelating ligands) has been synthesized and characterized on the basis of IR, NMR and 119Sn-Mössbauer studies. In the present study, an attempt was made to determine the comparative antiproliferative and antitumor effect of diorganotin(IV) complexes with different alkyl groups [Me2SnCl2.L1 (OTC-1), Et2SnCl2.L2 (OTC-2) and (n)Bu2SnCl2.L2 (OTC-3)]. The present study in human lymphocytes demonstrated that these diorganotin(IV) complexes could block the cell cycle progression and induce sister chromatid exchanges (SCEs) significantly, however, with respect to the induction of chromosome aberrations (CAs) it was very mild. Both the levels of p53 and p16 proteins were raised after diorganotin(IV) treatment and such induction was maximum in the OTC-3 treated samples. The antitumor activity was determined in accordance with the US National Cancer Institute (NCI) standard protocol for primary screening in Dalton's lymphoma that was maintained by serial intraperitoneal transplantation. The T/C (treated/control) value was increased (186% with OTC-3) when diorganotin(IV) was given after transplantation. The data suggest that the OTC-3 has better antiproliferative and antitumor activity and endogenous glutathione level has no influence on the effect of OTC-3.