rhazinicine and rhazinilam

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.

Topics: Aldehydes; Alkaloids; Alstonia; Animals; Antineoplastic Agents, Phytogenic; Aorta; Carbazoles; Cell Line, Tumor; Crystallography, X-Ray; Drug Evaluation, Preclinical; Heterocyclic Compounds, 4 or More Rings; Humans; Indole Alkaloids; Indolizines; Lactams; Molecular Structure; Phenylephrine; Pyrans; Pyridines; Rats; Secologanin Tryptamine Alkaloids; Vasodilator Agents

Topics: Alkaloids; Apocynaceae; Catalysis; Cyclization; Gold; Heterocyclic Compounds, 4 or More Rings; Indolizines; Lactams; Stereoisomerism

Eight new indole alkaloids (1-8) belonging to the rhazinilam-leuconolam-leuconoxine group, in addition to 52 other alkaloids, were isolated from the stem-bark extract of Leuconotis griffithii, viz., nor-rhazinicine (1), 5,21-dihydrorhazinilam-N-oxide (2), 3,14-dehydroleuconolam (3), and leuconodines A-E (4-8). The structures of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 1, 5, and 7 showed only moderate to weak cytotoxicity toward KB cells (IC50 12-18 μg/mL), while 8 showed moderate activity in reversing MDR in vincristine-resistant KB cells.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Apocynaceae; Azepines; Crystallography, X-Ray; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Heterocyclic Compounds, 4 or More Rings; Humans; Indolizines; KB Cells; Lactams; Malaysia; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Bark; Vincristine

Eleven new indole alkaloids, in addition to the previously reported rhazinal (1), and 14 other known alkaloids, were obtained from the Malayan Kopsia singapurensis, viz., kopsiloscines A-F (2-7), 16-epikopsinine (8), kopsilongine- N-oxide (9), 16-epiakuammiline (10), aspidophylline A (11), and vincophylline (12). The structures of these alkaloids were determined using NMR and MS analyses. Rhazinal (1), rhazinilam (17), and rhazinicine (18) showed appreciable cytotoxicity toward drug-sensitive as well as vincristine-resistant KB cells, while kopsiloscines A (2), B (3), and D (5) and aspidophylline A (11) were found to reverse drug-resistance in drug-resistant KB cells.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indolizines; KB Cells; Lactams; Malaysia; Molecular Structure; Plants, Medicinal