RESUMEN
Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.
Asunto(s)
Antiinflamatorios/uso terapéutico , Benzotiazoles/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Inflamación/tratamiento farmacológico , Oxadiazoles/uso terapéutico , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/metabolismo , Benzotiazoles/síntesis química , Benzotiazoles/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/metabolismo , Humanos , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/metabolismo , Relación Estructura-ActividadRESUMEN
On the basis of high binding affinity of 2-hexynyl-N(6)-methyladenosine and N(6)-substituted-4'-thioadenosine derivatives at the A3 adenosine receptor (AR), novel 2-alkynyl-substituted-N(6)-methyl-4'-thioadenosine derivatives, combining the characteristics of two classes of nucleosides were designed and synthesized from D-gulonic gamma-lactone via palladium-catalyzed cross coupling reaction as a key step. Among compounds tested, only compound 3b showed moderate binding affinity at the human A3 adenosine receptor without binding affinities at other subtypes.
Asunto(s)
Adenosina/análogos & derivados , Receptores Purinérgicos P1/metabolismo , Tionucleósidos/síntesis química , Adenosina/síntesis química , Adenosina/metabolismo , Animales , Células CHO , Catálisis , Cricetinae , Cricetulus , Diseño de Fármacos , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Paladio , Espectrofotometría Ultravioleta , Tionucleósidos/metabolismoRESUMEN
In view of biological activities of tiazofurin and azido or aminosugar nucleosides, novel azido- and amino-substituted tiazofurin derivatives (1 and 2) were efficiently synthesized starting from 1,2;5,6-di-O-isopropylidene-D-glucose.