In vitro antiproliferative effects, toxicity profiles in vivo in mice and antitumour activity in tumour-bearing mice of four diorganotin compounds

The in vitro antiproliferative effects, the in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screened for four novel di-n-butyltin carboxylates, di-n-butyltin bis(2,4-dihydroxybenzoate) [compound 1 (C1)], di-n-butyltin bis(2,5-dihydroxybenzoate) (C2), di-n-butyltin bis(pentafluorophenylacetate) (C3), and bis[di-n-butyl(pentafluorophenylacetato)tin] oxide (C4). All compounds revealed similar in vitro chemosensitivities in two cell lines, C26-10 and C26-A, two murine undifferentiated colon carcinoma cell lines. With all compounds tested, not only was cell growth inhibited in vitro, but also cell kill was achieved. At their maximum tolerated dose (MTD), C1 and C4 were inactive in vivo against colon 26 tumours in Balb/C mice when administered twice with one week interval (qd7x2 schedule). At their MTD, compound 2 (single dose administration and qd7x2 schedule) and compound 3 (qd7x2) showed slight in vivo antitumour activity with a ratio of the relative tumour size of the treated mice to that of control mice (T/C) = ca. 0.6 (T/C less than or equal to 0.6 being the cut-off level for sensitivity). However, the cut-off level for the growth delay factor (GDF) (>1) was not reached. With the exception of C2 administered with a single dose and C3 with the 2 doses protocol, treatment with these compounds did not increase the life span of the mice. Repeated administration of compound 2 did not improve the antitumour activity compared to single dose administration. This was probably due to the higher toxicity when C2 was administered a second time after one week.