In vitro cytotoxic activity of tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo

Abstract

The cytotoxicity in vitro and antitumor activity in vivo of the organotin compound tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) have been investigated. The IC50 values obtained in a panel of tumor cell lines were compared to those of the parental compound IST-FS 29 in the same cells. IST-FS 35 resulted significantly more active than IST-FS 29 with IC50 values in the range 0.16-1.8 microM. Toxicity studies in vivo, after intravenous administration of escalating concentrations of IST-FS 35, provided the identification of the maximal tolerated dose (3.5 mg/kg) which was employed as therapeutic dose in the antitumor activity experiments. Preliminary results, in transplanted murine tumor models, revealed that both the P388 myelomonocytic leukaemia and the B16-F10 melanoma, implanted subcutaneously in BDF1 mice, were inhibited about 96% in their tumor volume at day 11, following a single intravenous injection of the compound. Additional studies are mandatory to unravel the mechanism of action for the development of IST-FS 35 as potential antitumor drug.

Tin(IV) Schiff base complexes derived from pyridoxal: Synthesis, spectroscopic properties and cytotoxicity

“…The toxic effects of 3a – 3 k were compared with those induced by the analogous pyridoxamine organotin complexes that were orally administered; the results obtained in this study demonstrated that, after acute intraperitoneal administration, pyridoxal complexes 3a – 3 k are more potent than the pyridoxamine organotin complexes described previously, which cause lethality at doses from 200 to 300 mg kg −1 body weight. Moreover, complexes 3a – 3k and 4a – 4c are less toxic than tri‐ n ‐butyltin(IV)lupinylsulfide hydrogen fumarate (LD 50 = 5.40 mg kg −1 ) …”

Organotin Polyethers as Biomaterials

“…Most of the efforts related to anticancer activity have involved the use of monomeric or small molecules [25,26,27,28]. Monomeric organotin compounds have been studied since 1929 as potential anticancer agents.…”

Molecular basis of the interaction of novel tributyltin(IV) 2/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with an improved cytotoxic profile: Synthesis, structure, biological efficacy and QSAR studies

“…The tributyltin(IV)-3,4-diaminobenzoate, 3,5-diaminobenzoate and 2- [4-(dimethylamino) phenylazo]benzoate were also found to be promising cytostatic agents in vitro when tested against human cell line A549 (lung adenocarcinoma) [15]. The cytotoxicity of a tributyltin(IV) lupinylsulfide hydrogen fumarate has also been studied and proved to be extremely active when tested in vitro against a panel of tumor cell lines (MCF7, MDA-MB-231 (breast), A2780, OVCAR-3 (ovary), DBTRG-0.5MG, U87 MG, U373 MG, A-172 (glioma) and a mouse glioma cell line (GL261)) and in vivo against P388 (myelomonocytic leukemia) and the B16-F10 (melanoma) cell lines [16].…”