Synthesis and characterization of diorganotin(IV) complexes ofN-(2-pyridylmethylene)arylamines and mutagenicity testingin vivo of Et2SnCl2�[L4=N-(2-pyridylmethylene)-4-toluidine]

Abstract

Diorganotin(IV) dichloride complexes of the type R2SnCl2·L (R = methyl, ethyl, vinyl, t‐butyl, n‐butyl or phenyl; L = N‐(2‐pyridylmethylene)arylamine) have been synthesized and characterized on the basis of IR, NMR and 119Sn Mössbauer studies. Investigation of the complexes indicated that N‐(2‐pyridylmethylene)arylamines form distorted trans‐octahedral complexes with R2SnCl2 similar to the well‐known R2SnCl2·L. Cytogenetic toxicology testing has been performed for Et2SnCl2·L4 [L4 = N‐(2‐pyridylmethylene)‐4‐toluidine] in mouse bone‐marrow cells in vivo since such testing is a regulatory requirement before new drugs are released. This tin compound induced delay in cell‐cycle kinetics and sister chromatid exchanges (SCEs) significantly. The effect of Et2SnCl2·L4 was greater when endogenous glutathione (GSH) was depleted by buthionine sulphoximine (BSO). It seems that Et2SnCl2·L4 induces SCEs due to formation of adduct by binding on DNA which could interfere in DNA synthesis and cause delay in cell proliferation. Depletion of GSH could reduce the shielding effect of GSH on chromatin and allows more Et2SnCl2·L4 to bind on DNA. © 1998 John Wiley & Sons, Ltd.

p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin(IV) compounds

“…L The diorganotin(IV) dichloride complexes of N-(2-pyridylmethylene)arylamine, e.g., Me 2 SnCl 2 .L 1 (OTC-1), Et 2 SnCl 2 . L 2 (OTC-2) and n Bu 2 SnCl 2 .L 2 (OTC-3) were synthesized as previously described [8]. The stock solutions of OTC-1, OTC-2 and OTC-3 were prepared in 5% (v/v) ethanol/water keeping a concentration of 3 mg ml −1 .…”

“…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 2.39A°which in turn determines the formation of a tin-DNA complex [7]. In view of these, a series of diorganotin(IV) dichloride complexes of N-(2-pyridyl-methylene)arylamine (nitrogen chelating ligands) have been synthesized and characterized on the basis of IR, NMR and 119 Sn-Mössbauer studies [8,9]. The observed Sn-N bond lengths in Me 2 SnCl 2 .…”

“…L 2 and n Bu 2 SnCl 2 . L 2 have been investigated both in vivo and in vitro [8][9][10]. The data suggest that the n Bu 2 SnCl 2 .…”