RESUMEN
Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor (GPCR). Few synthetic agonists have been reported so far for class-B GPCRs. Here, we report the first scaffold compounds of ago-allosteric modulators for human GLP-2R, derived from methyl 2-{[(2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1).
Asunto(s)
Benzoatos/farmacología , Receptores de Glucagón/agonistas , Tiofenos/farmacología , Benzoatos/síntesis química , Benzoatos/química , Relación Dosis-Respuesta a Droga , Receptor del Péptido 2 Similar al Glucagón , Humanos , Estructura Molecular , Relación Estructura-Actividad , Tiofenos/síntesis química , Tiofenos/químicaRESUMEN
Eight new indole alkaloids, alpneumines A-H (1-8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells.
Asunto(s)
Alstonia/química , Antineoplásicos Fitogénicos/química , Alcaloides Indólicos/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Alcaloides Indólicos/aislamiento & purificación , Alcaloides Indólicos/uso terapéutico , Espectroscopía de Resonancia Magnética , Melanoma Experimental/tratamiento farmacológico , Ratones , Conformación Molecular , Vincamina/análogos & derivados , Vincamina/química , Vincamina/uso terapéuticoRESUMEN
Two new bisindole alkaloids, biscarpamontamine A (1), possessing an aspidosperma-iboga-type skeleton, and biscarpamontamine B (2), having an aspidosperma-aspidosperma-type skeleton, were isolated from stems of Tabernaemontana sphaerocarpa, and their structures were elucidated on the basis of spectroscopic data analysis. The absolute configuration of biscarpamontamine B (2) was established by comparison of its CD spectrum and with that of vobtusine (3). Biscarpamontamine B (2) showed potent cytotoxicity against various human cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Aspidosperma/química , Alcaloides Indólicos/aislamiento & purificación , Plantas Medicinales/química , Tabernaemontana/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Indonesia , Estructura Molecular , Tallos de la Planta/químicaRESUMEN
Five new alkaloids, alstilobanines A (1)-E (5) were isolated from Alstonia angustiloba (Apocynaceae) and their structures were determined by MS and 2D NMR spectral analysis. Alstilobanines A-E showed a moderate vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.
Asunto(s)
Alstonia/química , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Animales , Espectroscopía de Resonancia Magnética , Masculino , Modelos Moleculares , Estructura Molecular , Ratas , Ratas Wistar , Relación Estructura-Actividad , Vasodilatación/efectos de los fármacosRESUMEN
Two novel alkaloids with an unprecedented tricyclic skeleton, cassiarins A (1) and B (2), have been isolated from the leaves of Cassia siamea, and the structures were elucidated on the basis of spectroscopic data. Cassiarin A (1) showed a potent antiplasmodial activity.
Asunto(s)
Antimaláricos/química , Cassia/química , Compuestos Heterocíclicos con 3 Anillos/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/farmacología , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Pruebas de Sensibilidad ParasitariaRESUMEN
Two novel C(27)N(3)-type Lycopodium alkaloids, cryptadines A (1) and B (2) consisting of two octahydroquinoline rings (C(11)N) and a piperidine ring (C(5)N), have been isolated from the club moss Lycopodium cryptomerinum, and their structures and relative stereochemistry were elucidated on the basis of spectroscopic data, chemical transformations, and computational methods. Cryptadines A (1) and B (2) exhibited an inhibitory activity against acetylcholinesterase.
Asunto(s)
Alcaloides/química , Lycopodium/química , Piperidinas/química , Quinolinas/química , Alcaloides/aislamiento & purificación , Simulación por Computador , Ciclización , Espectroscopía de Resonancia Magnética , Estructura Molecular , Piperidinas/aislamiento & purificación , Quinolinas/aislamiento & purificaciónRESUMEN
Two novel indole alkaloids, alsmaphorazines A and B, were isolated from the leaves of Alstonia pneumatophora (Apocynaceae), and their structures were determined on the basis of the 2D NMR and MS spectral analysis. These alkaloids possessed a new skeleton consisting of an 1,2-oxazinane and an isoxazolidine chromophore. The absolute configuration of alsmaphorazine B was determined by using CD spectral analysis. Alsmaphorazine A inhibited the NO production in the LPS-stimulated J774.1 cells dose-dependently without affecting the cell viability.
Asunto(s)
Alstonia/química , Alcaloides Indólicos/química , Modelos Moleculares , Estructura MolecularRESUMEN
A novel tetrakis monoterpene indole alkaloid, alasmontamine A (1) consisting of bis-vobtusine-type skeletons, was isolated from the leaves of Tabernaemontana elegans. The structure including the relative stereochemistry was elucidated on the basis of spectroscopic data. Alasmontamine A (1) exhibited moderate cell growth inhibitory activity against HL-60 cells.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Alcaloides de Triptamina Secologanina/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/farmacología , Tabernaemontana/químicaRESUMEN
Three new Lycopodium alkaloids, carinatumins A-C (1-3), have been isolated from the club moss Lycopodium carinatum. Structures and stereochemistry of 1-3 were elucidated on the basis of 2D NMR correlations. Carinatumins A (1) and B (2) exhibited a potent inhibitory activity against acetylcholinesterase.
Asunto(s)
Carbenicilina/análogos & derivados , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Lycopodium/química , Piridonas/aislamiento & purificación , Alcaloides/química , Alcaloides/aislamiento & purificación , Carbenicilina/aislamiento & purificación , Carbenicilina/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Plantas Medicinales/química , Piridonas/farmacología , EstereoisomerismoRESUMEN
Eight stilbenoids, 1-(p-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (1), 2,7-dihydroxy-1,3-bis(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene (2), 4,7-dihydroxy-1-(p-hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene (3), 3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl (4), 3',5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (5), blestriarenes B (6) and C (7), and blestrianol A (8) have been isolated by the guidance of inhibitory effect of tubulin polymerization from the tubers of Bletilla striata (Orchidaceae). Among them, both of bisbenzyls 4 and 5 inhibited the polymerization of tubulin at IC(50) 10muM, respectively. Furthermore bisbenzyl 4 potentiated the cytotoxicity of SN-38 in BCRP-transduced K562 (K562/BCRP) cells.