Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.

Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. It is selectively expressed in vascular cells of blood vessels, but it is also circulating in blood plasma. SSAO activity in plasma is increased in some diseases associated with vascular complications and its catalytic products may cause tissue damage. We examined the effect of the oxidation of the SSAO substrate, methylamine, on cultured smooth muscle cells. Cell incubation with methylamine plus soluble SSAO, contained in bovine serum, resulted toxic to rat aorta A7r5 and human aortic smooth muscle cells, as measured by MTT reduction. This effect was completely reverted by specific SSAO inhibitors, indicating that the toxicity was mediated by the end products generated. Moreover, SSAO-mediated deamination of methylamine induced apoptosis in A7r5 cells, detected by chromatin condensation, Caspase-3 activation, PARP cleavage and cytochrome c release to cytosol. Formaldehyde, rather than H2O2, resulted to be a strong apoptotic inducer to A7r5 cells. Taken together, the results suggest that increased plasma SSAO activity in pathological conditions, could contribute to apoptosis in smooth muscle cells, leading to vascular tissue damage.

No abstract

New stibine and bismuthine substituted thienyl ring compounds, i.e. tris(3-methyl-2-thienyl)stibine (1), tris(3-methyl-2-thienyl)bismuthine (2), tris(3-thienyl)stibine (3), tris(3-thienyl)bismuthine (4) and tris(5-chloro-2-thienyl)stibine (5), have been synthesized and characterized by IR, mass, 1 H, 13 C, COSY, and HETCOR NMR spectroscopy. The metal centres in all compounds are pyramidal, and molecules in the stibine compound (1) and bismuthine compound (2) associate via Sb· · ·S or Bi· · ·S interactions to form supramolecular chains.The cytotoxicity of compounds 1 and 5 was determined. For compound 5, 85% of carcinogenic cell growth inhibition (U, K and H) was observed. Compound 1 shows a significant selectivity (>80%) for carcinogenic cell growth (K and U) inhibition. Both the compounds are highly toxic for the growth of normal lymphocytes with ∼95% lethality. Compound 1 is approximately 20 times more toxic than 5 against Artemia salina.

El combat de Raïmats, succeït el darrer dia de la batalla de l’Ebre (15 de novembre de 1938) ha estat investigat des de diverses òptiques per part del grup de recerca DIDPATRI en una perspectiva interdisciplinar i transversal. La recerca va començar amb una petició de l’associació cívica Lo Riu el 2013 a la Universitat de Barcelona que van aconduir a una intensa campanya arqueològica en una clara dinàmica de recerca pública. En els anys posteriors i fins el 2018 les accions sobre Raïmats s’han multiplicat incorporant experiències sobre museografia a l’aire lliure;  visites escolars; turisme de camps de batalla; recreació històrica i generació d’iconografia didàctica. Tot plegat la dinàmica no exhaurida, es contextualitza també en una dinàmica pedagògica d’investigació acció en la qual els plantejaments didàctics assoleixen protagonisme. L’experiència transversal de Raïmats incorpora també una vessant explícita de memòria en tant que el lloc s’ha convertit en un referent significatiu de la batalla de l’Ebre.