IN-VITRO ANTIPROLIFERATIVE EFFECTS, TOXICITY PROFILES IN-VIVO IN MICEAND ANTITUMOR-ACTIVITY IN TUMOR-BEARING MICE OF 4 DIORGANOTIN COMPOUNDS

The in vitro antiproliferative effects, the in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screen ed for four novel di-n-butyltin carboxylates, di-n-butyltin bis(2,4-di hydroxybenzoate) [compound 1 (C1)], di-n-butyltin bis(2,5-dihydroxyben zoate) (C2), di-n-butyltin bis(pentafluorophenylacetate) (C3), and bis [di-n-butyl(pentafluorophenylacetato)tin] oxide (C4). All compounds re vealed similar in vitro chemosensitivities in two cell lines, C26-10 a nd C26-A, two murine undifferentiated colon carcinoma cell lines. With all compounds tested, not only was cell growth inhibited in vitro, bu t 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 mic e 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 con trol 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 adm inistered with a single dose and C3 with the 2 doses protocol, treatme nt with these compounds did not increase the life span of the mice. Re peated administration of compound 2 did not improve the antitumour act ivity compared to single dose administration. This was probably due to the higher toxicity when C2 was administered a second time after one week.