Angustine

Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis.[Pubmed:25636869]

Phytomedicine. 2015 Jan 15;22(1):45-8.

Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), Angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 muM. Angustidine (2), nauclefine (3), Angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 muM.

Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors.[Pubmed:23261030]

Phytochemistry. 2013 Feb;86:8-20.

Thirteen Psychotria alkaloids were evaluated regarding their interactions with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A and MAO-B), which are enzymatic targets related with neurodegenerative diseases. Two quaternary beta-carboline alkaloids, prunifoleine and 14-oxoprunifoleine, inhibited AChE, BChE and MAO-A with IC(50) values corresponding to 10 and 3.39 muM for AChE, 100 and 11 muM for BChE, and 7.41 and 6.92 muM for MAO-A, respectively. Both compounds seem to behave as noncompetitive AChE inhibitors and time-dependent MAO-A inhibitors. In addition, the monoterpene indole alkaloids (MIAs) Angustine, vallesiachotamine lactone, E-vallesiachotamine and Z-vallesiachotamine inhibited BChE and MAO-A with IC(50) values ranging from 3.47 to 14 muM for BChE inhibition and from 0.85 to 2.14 muM for MAO-A inhibition. Among the tested MIAs, Angustine is able to inhibit MAO-A in a reversible and competitive way while the three vallesiachotamine-like alkaloids display a time-dependent inhibition on this target. Docking calculations were performed in order to understand the binding mode between the most active ligands and the selected targets. Taken together, our findings established molecular details of AChE, BChE and MAO-A inhibition by quaternary beta-carboline alkaloids and MIAs from Psychotria, suggesting these secondary metabolites are scaffolds for the development of multifunctional compounds against neurodegeneration.

Naucline, a new indole alkaloid from the bark of Nauclea officinalis.[Pubmed:22469596]

Molecules. 2012 Apr 2;17(4):4028-36.

A new indole alkaloid, naucline (1) together with four known alkaloids, Angustine (2), angustidine (3), nauclefine (4) and naucletine (5), were isolated from the bark of Nauclea officinalis. The structures of all isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS-IT-TOF. In addition to that of alkaloid 1, the complete 13C-NMR data of naucletine (5) were also reported. Naucline (1) showed a moderate vasorelaxant activity (90% relaxation at 1 x 10(-5) M) whereas, Angustine (2), nauclefine (4), and naucletine (5) showed potent vasorelaxant activity (more than 90% relaxation at 1 x 10(-5) M) on an isolated rat aorta.

[Alkaloids from the leaves of Nauclea officinalis].[Pubmed:20939184]

Yao Xue Xue Bao. 2010 Jun;45(6):747-51.

To study chemical constituents of the leaves of Nauclea officinalis, eight alkaloids were isolated from 95% ethanol extract by various chromatographic methods. The structures were elucidated on the basis of spectroscopic data (IR, UV, ESI-MS, 1D and 2D NMR) and identified as naucleactonin C (1), strictosamide (2), vincosamide (3), pumiloside (4), angustoline (5), Angustine (6), 18, 19-dihydroAngustine (7) and naucleofficine D (8). Compound 1 is a new indole alkaloid. Compounds 6 and 7 were isolated from this plant for the first time.

Novel bis(monoterpenoid) indole alkaloids from Psychotria bahiensis.[Pubmed:12828456]

J Nat Prod. 2003 Jun;66(6):752-4.

Two new bis(monoterpenoid) indole alkaloid glucosides, bahienoside A (1) and bahienoside B (2), together with five known compounds, 5alpha-carboxystrictosidine, Angustine, strictosamide, and (E)- and (Z)-vallesiachotamine, were isolated from the aerial parts of Psychotria bahiensis collected in Trinidad, West Indies. The structures of the compounds were elucidated using 1D and 2D NMR spectral methods, viz., (1)H, (13)C, (13)C DEPT, (1)H-(1)H COSY, HSQC, HMQC, HMBC, and TOCSY aided by IR, UV, and circular dichroism measurements.

New indole alkaloids from Sarcocephalus latifolius.[Pubmed:11547422]

Nat Prod Lett. 2001;15(1):43-8.

Phytochemical investigation of the root extract of Sarcocephalus latifolius has led to the isolation of the new indole alkaloids 21-O-methylstrictosamide aglycone and 21-O-ethylstrictosamide aglycone, together with strictosamide, Angustine, nauclefine, angustidine, angustoline, 19-O-ethylangustoline, naucleidinal, 19-epi-naucleidinal, quinovic acid-3 beta-O-beta-D-fucopyranoside, quinovic acid-3 beta-O-alpha-L-rhamnopyranoside, scopoletin, and beta-sitosterol. Strictosamide displayed moderate antiplasmodial activity against Plasmodium falciparum.

Indole alkaloids with in vitro antiproliferative activity from the ammoniacal extract of Nauclea orientalis.[Pubmed:1620742]

Planta Med. 1992 Feb;58(1):43-8.

Nine Angustine-type alkaloids were isolated from ammoniacal extracts of Nauclea orientalis L. (Rubiaceae). Three of them, 10-hydroxyAngustine and the two diastereoisomeric 3,14-dihydroangustolines, have not been described in the literature thus far. The structures of the isolates were determined with spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy. The compounds were found to exhibit in vitro anti-proliferative activity against the human bladder carcinoma T-24 cell line and against EGF (epidermal growth factor)-dependent mouse epidermal keratinocytes. By using overpressure layer chromatography, it was shown that minor quantities of these alkaloids occur in dried Nauclea orientalis leaves. The use of ammonia in the extraction process results in a significant increase in the formation of Angustine-type alkaloids from strictosamide-type precursors.

South American Strychnos species. Ethnobotany (except curare) and alkaloid screening.[Pubmed:2179633]

J Ethnopharmacol. 1990 Feb;28(1):1-52.

The ethnobotanical uses of South American species of Strychnos L. (Loganiaceae) are reviewed, with the exception of their major role in the preparation of curare, which will be dealt with in detail elsewhere. Medicinal uses are less common than is the case with the African and Asian species of the genus. About 140 samples, mostly of leaves, belonging to 53 species, have been screened for alkaloids. As with species from other parts of the world, the stem bark and root bark tend to be a richer source than leaves. Nor-harman is present in extracts from S. barnhartiana leaves. Pyridino-indolo-quinolizidinone (Angustine-type) bases are also found in several species. The occurrence and pharmacology of the (non-curarizing) alkaloids known to be present in South American Strychnos species is reviewed.