RESUMO
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.
Assuntos
Manose/análogos & derivados , Nucleosídeos/síntese química , Tiazóis/síntese química , Triazóis/síntese química , Manose/química , Nucleosídeos/química , Relação Estrutura-Atividade , Tiazóis/química , Triazóis/químicaRESUMO
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.
Assuntos
Adenosina/síntese química , Adenosil-Homocisteinase/efeitos adversos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Adenosina/análogos & derivados , Adenosina/química , Adenosina/farmacologia , Indicadores e Reagentes , Cinética , Modelos Moleculares , Conformação MolecularRESUMO
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.
Assuntos
Furanos , Nucleosídeos de Pirimidina/síntese química , Indicadores e Reagentes , Modelos Moleculares , Nucleosídeos de Pirimidina/químicaRESUMO
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.
Assuntos
Antineoplásicos/síntese química , Azacitidina/análogos & derivados , Azacitidina/síntese química , Antineoplásicos/química , Azacitidina/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indicadores e Reagentes , Estrutura Molecular , Células Tumorais CultivadasRESUMO
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.
Assuntos
Adenosina/síntese química , Adenosil-Homocisteinase/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Adenosina/análogos & derivados , Adenosina/química , Adenosina/farmacologia , Desenho de Fármacos , Indicadores e Reagentes , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Furanos/química , Timina/síntese química , Timina/farmacologia , Linhagem Celular , Testes de Sensibilidade Microbiana , Timina/química , Vírus/efeitos dos fármacosRESUMO
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.
Assuntos
Adenosina/análogos & derivados , Adenosina/química , Adenosina/metabolismo , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/metabolismo , Receptores Purinérgicos P1/metabolismo , Animais , Células CHO , Cricetinae , Desenho de Fármacos , Cinética , Ligantes , Ligação Proteica , Agonistas do Receptor Purinérgico P1 , Ensaio Radioligante , Ratos , Receptor A3 de Adenosina , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/metabolismo , Relação Estrutura-AtividadeRESUMO
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]