Toxicity Profiles In Vivo in Mice and Antitumour Activity in Tumour-Bearing Mice of Di- and Triorganotin Compounds

M Gielen,H Dalil,R Willem,G J Peters,C M Kuiper,D De Vos

doi:10.1155/mbd.1998.83

Abstract

The in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screened for four di-n-butyltin and five triorganotin carboxylates, di-n-butyltin diterebate (5), bis(phenylacetate) (6), bis(deoxycholate) (7), bis(lithocholate) (8), tri-n-butyltin terebate (9), cinnamate (10), and triphenyltin terebate (11). At their maximum tolerated dosis (MTD), no antitumour effect (T/C ~1) was observed for the compounds 5, 7, 9, 10 and 11. The compounds 6 (T/C = 0.51) and 8 (T/C = 0.42) showed clear antitumour activity after single dose administration and might therefore be of interest for further antitumour activity studies.

Highlights

Organotin carboxylates often exhibit significant in vitro antitumour activities (Bou&lam, 1992)(Bou&lam, 1993)(Gielen, 1996a)(Gielen, 1996b)(Gielen, 1996c)
Antitumour activity was evaluated by calculation of the T/C
Initial dose-finding studies were performed with groups of 2 mice which were treated weekly for two weeks by i.p. injection

Summary

Introduction

Organotin carboxylates often exhibit significant in vitro antitumour activities (Bou&lam, 1992)(Bou&lam, 1993)(Gielen, 1996a)(Gielen, 1996b)(Gielen, 1996c). The in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice (Gielen, 1995) were screened for four din-butyltin carboxylates, di-n-butyltin bis(2,4-dihydroxybenzoate) (1), bis(2,5-dihydroxybenzoate). Cell growth was inhibited in vitro, and cell kill was achieved. At their maximum tolerated dose (MTD), 1 and were inactive in vivo against colon 26 tumours in Balb/C mice whereas compounds 2 and 3 showed slight in vivo antitumour activity. Repeated administration of compound 2 did not improve the antitumour activity compared to single dose administration. An additional set of compounds, active in vitro, four di-n-butyltin and five triorganotin carboxylates, namely di-n-butyltin diterebate (5) (Gielen, 1997), bis(phenylacetate) (6), bis(deoxycholate) (7).

Materials and Methods

Results and discussion

Conclusions