X-Ray Structure and In Vitro Anti-Tumoural Activity of the Dimeric Bis[(2-Phenyl-1,2-Dicarba-Closo-Dodecaborane-1-Carboxylato)-Di-n-Butyltin] Oxide.

X-ray diffraction studies reveal the structure of {[(2-C(6)H(5)-1,2-C(2)B(10)H(10)-1-COO)Bu(2)Sn](2)O}(2), 1, to conform to the common motif found for {[(R'COO)R(2)Sn](2)O}(2) compounds. The dimer features a central Bu(2)Sn(2)O(2) unit (two-fold symmetry) with the two Bu(2)Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu(2)Sn moiety. The two pairs of exo- and endo-cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti-tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2-methylcarboranylacetate, derivative 2, and with clinically used compounds.

Di-n-Butyl-, Tri-n-Butyl- and Triphenyltin dl-Terebates: Synthesis, Characterization and In Vitro Antitumour Activity.

Di-n-butyltin, tri-n-butyltin and triphenyltin terebates were screened against several human tumour cell lines and found comparably or more active than carboplatin, cis-platin, 5-fluorouracil, methotrexate and doxorubicin, some reference compounds used clinically.

Triphenyltin ortho-aminophenyl- and 2-pyridyl-thiolates: synthesis and in vitro antitumour activity.

The synthesis, spectroscopic characterization and in vitro antitumour activity of two triorganotin compounds, triphenyltin ortho-aminophenylthiolate (1) and triphenyltin 2-pyridylthiolate, compound (2) are reported. The structure of 1 is confirmed by X-ray diffraction, with the tin atom in a distorted tetrahedral geometry because of monodentate coordination, as a thiolate (Sn-S 2.431(2) A), of the ortho-aminophenylthiolate ligand. The in vitro antitumour activities of 1 and 2, against a number of cell lines, are comparable to those exhibited by methotrexate and doxorubicin, and higher than those of carboplatin and cisplatin.

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.

In vitro antiproliferative effects, toxicity profiles in vivo in mice and antitumour activity in tumour-bearing mice of five organotin compounds.

The in vitro antiproliferative effects, the toxicity profiles in vivo in mice and the antitumour activity in tumour-bearing mice were screened for five recently synthesized organotin compounds: triphenyltin 5-sulfosalicylate (1), triphenyltin 5-aminosalicylate (2), triphenyltin 4-fluorobenzoate (3), tri-n-butyltin 2,6-difluorobenzoate (4) and di-n-butyltin bis (2,5-dihydroxybenzoate) (5). The in vitro chemosensitivity tests showed that compound 1 has the lowest antiproliferative effect in C26-10. In WiDr, compounds 1 and 5 were less active than the other compounds tested. The IC50 for cisplatin in C26-10 was in the same range as for 1. For compound 3 a steep dose response curve in C26-10 turned out to be remarkably different from the curves of the other compounds. In vivo, compound 1 was most toxic, mainly through paralysis. At their maximum tolerated dose (MTD) for single administration compounds 1, 2, 3 and 4 are inactive against murine colon carcinoma Colon 26. At a single administration, compound 5 was the most active compound with Test/Control ratio (T/C) below 0.6 and Growth Delay Factor (GDF) above 1.0, their respective cut-off levels for sensitivity.

Synthesis, characterization and high in vitro antitumour activity of novel triphenyltin carboxylates.

The synthesis and spectral characterization of six novel triphenyltin compounds are described. The in vitro antitumour activity of three of these compounds against two human tumour cell lines, MCF-7, a mammary tumour, and WiDr, a colon carcinoma, was determined. All three compounds are more active than cis-platin, etoposide and doxorubicin against both tumour cell lines. They are as active as mitomycin C against WiDr, but less active against MCF-7.