RESUMEN
Bone marrow-derived mesenchymal stem cells (BM-MSCs) possess excellent therapeutic potential for the treatment of various diseases including graft-versus-host disease, rheumatoid arthritis, osteoarthritis, and multiple sclerosis. Here, we generated an induced pluripotent stem cell (iPSC) line from BM-MSCs employing a non-integrating episomal vector. The generated iPSCs expressed pluripotency markers, showed a normal karyotype, and exhibited the potential for in vitro differentiation into three germ layers. This iPSC line can be used as a healthy control in stem cell therapeutics and disease modeling studies.
Asunto(s)
Células Madre Pluripotentes Inducidas , Células Madre Mesenquimatosas , Médula Ósea , Células de la Médula Ósea , Diferenciación Celular , HumanosRESUMEN
Many studies show that selective introduction of fluorine within pharmacological agents leads to improved activities. In this study, we determine the effects of aryl fluorine substitution in 5a-(benzylsulfanyl)-dihydrobicyclomycin (3) on the in vitro inhibition of Escherichia coli rho-dependent ATPase activity. Compound 3 is an analog of bicyclomycin (1), which is the only known selective inhibitor of rho, and 1 and 3 have comparable in vitro inhibitory activities. We demonstrate that aryl fluorine substitution of 3 leads to increase in inhibitory activity but that the beneficial effects due to fluorine were dependent upon the site and number of fluorine substituents. The bioactivities are rationalized in terms of the bond moment created by the aryl fluoride bond within the 5a-aryl dihydrobicyclomycin-rho-binding pocket. Use of this hypothesis led to the design of dihydrobicyclomycin derivatives with superior in vitro rho inhibitory activities.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Flúor/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Systematic investigations to develop an efficient enantioselective synthetic method for alpha-alkyl-alanine by catalytic phase-transfer alkylation were performed. The alkylation of 2-naphthyl aldimine tert-butyl ester, 1E, with RbOH and O(9)-allyl-N-2',3',4'-trifluorobenzylhydrocinchonidinium bromide, 6, at -35 degrees C showed the highest enantioselectivities, up to 96% ee.
RESUMEN
Twenty-seven N,N',N"-trisubstituted thiourea derivatives were prepared. Among them, 1-[3-(4'-hydroxy-3'-methoxy-phenyl)-propyl]-1,3-diphenethyl-thiourea (8l, IC(50)=0.32 microM), showed 2-fold higher antagonistic activity than that of capsazepine (3, IC(50)=0.65 microM) against the vanilloid receptor in a (45)Ca(2+)-influx assay.
Asunto(s)
Receptores de Droga/antagonistas & inhibidores , Tiourea/síntesis química , Animales , Animales Recién Nacidos , Calcio/metabolismo , Isótopos de Calcio , Capsaicina/análogos & derivados , Concentración 50 Inhibidora , Canales Iónicos/antagonistas & inhibidores , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratas , Relación Estructura-Actividad , Tiourea/farmacologíaRESUMEN
Twenty-one pyridine-2-carboxylate derivatives were prepared by the coupling of 6-formyl-2-carboxylic acid with the corresponding phenol, thiophenol, and aniline, substituted with various functional groups. Among them, the 3,4-dichlorothiophenol ester (9p) showed the highest in vitro telomerase inhibitory activity and quite significant in vivo tumor suppression activity.