Melanoma is a very aggressive type of skin cancer. Mutation in BRAF and NRAS are often found in patients with this disease. Therefore, in recent years the search for new molecules that inhibit these proteins has been intensified. After many years with no new treatments for melanoma, the U.S. Food and Drug Administration (FDA) recently approved vemurafenib. However, many patients have already acquired resistance and have experienced severe side effects. Therefore, this work aims to evaluate a new set of compounds including allylic isothiouronium salts (1, 2 and 3), N-phenyl-substituted analog (4) and isothiosemicarbazide salts (5 and 6) for their potential antimelanoma activity. To this end, viability assay, cell cycle analysis, expression of NRAS and BRAF, as well as migration and invasion assay were performed with different melanoma cell lines. Isothiouronium salts 1-3 presented CC50 (concentration required to reduce the cell number by 50%) in a range of 7-28 μM. Furthermore, salt 1 significantly decreased the expression of NRAS. However, cells incubated with these salts did not disturb the cell cycle phases; instead, an increase in the number of apoptotic cells was observed. Regarding potential antiinvasion effects, both 1 and 2 prevented cell migration as well as cell invasion. Finally, when salts 1 and 2 were associated with vemurafenib, a marked decrease in cell viability was observed when compared to the compounds incubated alone. Briefly, the salts exhibited interesting results, especially 1, which decreased the expression of NRAS, increased apoptotic cells and, when combined with vemurafenib, resulted in a synergistic effect. Therefore, we intend to test compound 1 in pre-clinical studies.
A straightforward synthesis of cyclopropylidene iminolactones mediated by triflic acid under mild conditions is described. Different types of hydroxy‐substituted cyclopropanecarboxamides containing a variety of functional groups participated in this smooth cyclization through an intramolecular SN2 attack of the amidic oxygen on the protonated carbinol group with the release of water. Ten cyclopropylidene iminolactones were readily obtained in high purity after a basic work‐up with no additional chromatographic separation (62–98 % yield). Besides the simplicity, the method is highly diastereoselective and tolerates several functional groups, demonstrating the broad scope of this process. Selected iminolactones were applied in further synthetic transformations to give functionalized cyclopropanecarboxamides through hydrogenolysis or nucleophilic ring‐opening reactions.
Cyclohexane derivatives Q 0040 Stille Reaction over cis-Halocyclohexadienediol Derivatives. -The reaction is examined with a view to building blocks for chiral epoxyenones, required in natural product synthesis. -(HEGUABURU*, V.; SA, M. M.; SCHAPIRO, V.; PANDOLFI, E.; Tetrahedron Lett. 49 (2008) 48, 6787-6790; Dep. Org. Chem., Fac. Chem., Univ. Rep., 11800 Montevideo, Urug.; Eng.) -Mais 10-056
Promoted by Molecular Sieves. -A new acetylation method of nucleosides is developed. Best results in yield and selectivity are achieved in the presence of potassium-exchanged molecular sieves under solvent-free conditions. Reactive functional groups like thiol and acetal are well tolerated. -(SA*, M. M.; MEIER, L.; Synlett 2006, 20, 3474-3478; Dep. Quim., Univ. Fed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.