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

Abstract

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.