RESUMO
Three series of the ß-pyrimidine alanines, including willardiine - a naturally occurring amino acid, were prepared from the l-serine-derived sulfamidates. Compounds 3b, 4a and 4b demonstrated antiproliferative activity toward the studied cancer cell lines, albeit the effect of these compounds on human brain astrocytoma MOG-G-CCM cells was more significant than on human neuroblastoma SK-N-AS cells. The cytosine analog of willardiine, compound 4b, reduced viability of MOG-G-CCM cells with EC50 = 36 ± 2 µM, more effectively than AMPA antagonist GYKI 52466. Willardiine showed possible capability of affecting invasiveness of glioblastoma U251 MG cells with no effect on their viability and morphology. Compound 3d, the ethyl ester of willardiine, featured activity toward binding domain hHS1S2I of the GluR2 receptor. Docking analysis revealed that the location mode of compound 3d at the S1S2 domain of hGluR2 (PDB ID: 3R7X) might differ from that of willardiine.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , beta-Alanina/análogos & derivados , beta-Alanina/farmacologia , Alanina/análogos & derivados , Alanina/síntese química , Alanina/química , Alanina/farmacologia , Antineoplásicos/síntese química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Pirimidinas/síntese química , Uracila/síntese química , Uracila/química , Uracila/farmacologia , beta-Alanina/síntese químicaRESUMO
A new, highly potent activator for molybdenum hexacarbonyl and 2-fluorophenol is described. An "instant"catalyst formed in situ from molybdenum hexacarbonyl and 2-fluorophenol shows high activity for cross- and ring-closing alkyne metathesis reaction. The use of 2-fluorophenol can be combined with other activation methods to allow alkyne metathesis at relatively low temperature (80 degrees C).
RESUMO
[reaction: see text] An improved "instant" catalyst for ring-closing alkyne metathesis reaction is described. Catalyst formed in situ from molybdenum hexacarbonyl and 2-fluorophenol can be used without exclusion of air and moisture and shows high activity in metathesis of functionalized diynes. This system allows cyclization of substrates which were incompatible with previously known Mo(CO)(6)/phenol catalysts.