ABSTRACT
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).
Subject(s)
Benzoates/pharmacology , Receptors, Glucagon/agonists , Thiophenes/pharmacology , Benzoates/chemical synthesis , Benzoates/chemistry , Dose-Response Relationship, Drug , Glucagon-Like Peptide-2 Receptor , Humans , Molecular Structure , Structure-Activity Relationship , Thiophenes/chemical synthesis , Thiophenes/chemistryABSTRACT
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.
Subject(s)
Alstonia/chemistry , Indole Alkaloids/chemistry , Models, Molecular , Molecular StructureABSTRACT
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.
Subject(s)
Alstonia/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Indole Alkaloids/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/therapeutic use , Indole Alkaloids/isolation & purification , Indole Alkaloids/therapeutic use , Magnetic Resonance Spectroscopy , Melanoma, Experimental/drug therapy , Mice , Molecular Conformation , Vincamine/analogs & derivatives , Vincamine/chemistry , Vincamine/therapeutic useABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Secologanin Tryptamine Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/pharmacology , Tabernaemontana/chemistryABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Aspidosperma/chemistry , Indole Alkaloids/isolation & purification , Plants, Medicinal/chemistry , Tabernaemontana/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Indonesia , Molecular Structure , Plant Stems/chemistryABSTRACT
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.
Subject(s)
Alstonia/chemistry , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Animals , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Molecular Structure , Rats , Rats, Wistar , Structure-Activity Relationship , Vasodilation/drug effectsABSTRACT
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.
Subject(s)
Alkaloids/chemistry , Lycopodium/chemistry , Piperidines/chemistry , Quinolines/chemistry , Alkaloids/isolation & purification , Computer Simulation , Cyclization , Magnetic Resonance Spectroscopy , Molecular Structure , Piperidines/isolation & purification , Quinolines/isolation & purificationABSTRACT
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.
Subject(s)
Antimalarials/chemistry , Cassia/chemistry , Heterocyclic Compounds, 3-Ring/chemistry , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Plasmodium falciparum/drug effects , Animals , Antimalarials/therapeutic use , Heterocyclic Compounds, 3-Ring/pharmacology , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Parasitic Sensitivity TestsABSTRACT
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.
Subject(s)
Carbenicillin/analogs & derivatives , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Lycopodium/chemistry , Pyridones/isolation & purification , Alkaloids/chemistry , Alkaloids/isolation & purification , Carbenicillin/isolation & purification , Carbenicillin/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Plants, Medicinal/chemistry , Pyridones/pharmacology , StereoisomerismABSTRACT
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.
