ABSTRACT
Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Alstonia/chemistry , Indole Alkaloids/chemistry , Aldehydes/chemistry , Aldehydes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Aorta/drug effects , Carbazoles/chemistry , Carbazoles/pharmacology , Cell Line, Tumor/drug effects , Crystallography, X-Ray , Drug Evaluation, Preclinical/methods , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Indole Alkaloids/pharmacology , Indolizines/chemistry , Indolizines/pharmacology , Lactams/chemistry , Lactams/pharmacology , Molecular Structure , Phenylephrine/pharmacology , Pyrans/chemistry , Pyrans/pharmacology , Pyridines/chemistry , Pyridines/pharmacology , Rats , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/pharmacology , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacologyABSTRACT
A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.
