Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety

Four alkaloids comprising two vallesamine, one strychnan, and pyranopyridine alkaloid were isolated from two Malayan Alstonia species, A. pneumatophora and A. rostrata. Several of the isolated alkaloids show antiproliferative (e.g., rhazinicine) and vasorelaxation (e.g., pneumatophorine, undulifoline) effects. [Display omitted] •Thirty-six alkaloids, four previously unknown, were isolated from two Alstonia species.•Pneumatophorine is notable for the incorporation of a 3-ethylpyridine moiety.•The alkaloids showed antiproliferation and vasorelaxation effects. 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.