RESUMEN
In view of biological activities of azole nucleosides and apio-dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3-O-isopropylidene-apio-beta-D-furanose (3), which was prepared from D-mannose.
Asunto(s)
Manosa/análogos & derivados , Nucleósidos/síntesis química , Tiazoles/síntesis química , Triazoles/síntesis química , Manosa/química , Nucleósidos/química , Relación Estructura-Actividad , Tiazoles/química , Triazoles/químicaRESUMEN
Halogenated analogues of neplanocin A were synthesized from the key intermediate 1, among which fluoro-neplanocin A was found to be novel mechanism-based irreversible inhibitor of S-Adenosylhomocysteine hydrolase.
Asunto(s)
Adenosina/síntesis química , Adenosilhomocisteinasa/efectos adversos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Adenosina/análogos & derivados , Adenosina/química , Adenosina/farmacología , Indicadores y Reactivos , Cinética , Modelos Moleculares , Conformación MolecularRESUMEN
Pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities. Thymine analogue 1 and its corresponding 2'-deoxy analogue 3 exhibited high cytotoxicity instead of giving antiviral activities.
Asunto(s)
Furanos , Nucleósidos de Pirimidina/síntesis química , Indicadores y Reactivos , Modelos Moleculares , Nucleósidos de Pirimidina/químicaRESUMEN
The bicyclic 3'-O,5'-C-methylene-linked and 2'-O,5'-C-methylene-linked 5-azacytidine derivatives were readily synthesized from 1,2;5,6-di-O-isopropylidene-D-glucose and evaluated against several cancer cell lines.
Asunto(s)
Antineoplásicos/síntesis química , Azacitidina/análogos & derivados , Azacitidina/síntesis química , Antineoplásicos/química , Azacitidina/química , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indicadores y Reactivos , Estructura Molecular , Células Tumorales CultivadasRESUMEN
A novel apio analogue of neplanocin A was efficiently synthesized from D-ribose via stereoselective aldol-retroaldol reaction for introducing hydroxymethyl group and RCM reaction for synthesizing carbocycle, and its inhibitory activity against SAH hydrolase was assayed.
Asunto(s)
Adenosina/síntesis química , Adenosilhomocisteinasa/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Adenosina/análogos & derivados , Adenosina/química , Adenosina/farmacología , Diseño de Fármacos , Indicadores y Reactivos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were successfully synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities against HIV-1, HIV-2, EMCV, Cox. B3 and VSV. Thymine analogue (5) and its corresponding 2'-deoxy analogue (6) exhibited high cytotoxicity instead of giving antiviral activities.
Asunto(s)
Furanos/química , Timina/síntesis química , Timina/farmacología , Línea Celular , Pruebas de Sensibilidad Microbiana , Timina/química , Virus/efectos de los fármacosRESUMEN
Several 3'-fluoro analogues, 1a, 1b, and 1c of selective and potent adenosine A(3) receptor agonist, Cl-IB-MECA were synthesized from D-xylose via highly regioselective opening of lyxo-epoxides, 8a and 8b with fluoride anion. Compared to the high binding affinity of Cl-IB-MECA to the A(3) adenosine receptor, the corresponding 3'-fluoro derivative showed remarkably decreased binding affinity, indicating that 3'-hydroxyl group acts as hydrogen bonding acceptor, not hydrogen bonding donor like fluorine atom in binding to the A(3) adenosine receptor.
Asunto(s)
Adenosina/análogos & derivados , Adenosina/química , Adenosina/metabolismo , Hidrocarburos Fluorados/síntesis química , Hidrocarburos Fluorados/metabolismo , Receptores Purinérgicos P1/metabolismo , Animales , Células CHO , Cricetinae , Diseño de Fármacos , Cinética , Ligandos , Unión Proteica , Agonistas del Receptor Purinérgico P1 , Ensayo de Unión Radioligante , Ratas , Receptor de Adenosina A3 , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/metabolismo , Relación Estructura-ActividadRESUMEN
A total synthesis of apio-neplanocin A, which combines properties of apio nucleoside and neplanocin A and is a potential inhibitor of S-adenosylhomocysteine hydrolase, was accomplished starting from D-ribose via stereoselective hydroxymethylation and RCM reaction. [reaction: see text]