Cytotoxic Yohimbine-Type Alkaloids from the Leaves of Rauvolfia vomitoria.

Two new yohimbine-type monoterpene indole alkaloids, rauvines A and B, and six known derivatives were obtained from the leaves of R. vomitoria. The structures of rauvines A and B were determined by extensive spectroscopic analyses, 13 C-NMR, and ECD calculations. This is the first time to determine the absolute configurations of yohimbine-type N-oxides by quantum chemistry calculations (13 C-NMR and ECD calculations). All the isolates were tested for their cytotoxicity against five human cancer cell lines. Rauvine B showed moderate cytotoxicity on human MCF-7 breast, SWS80 colon, and A549 lung cancer cell lines with IC50 values of 25.5, 22.6, and 26.0 µM, respectively.

Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria.

Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C22 yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 µM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC50 value of 16.39 ± 1.41 µM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.

Monoterpene indole alkaloids with diverse skeletons from the stems of Rauvolfia vomitoria and their acetylcholinesterase inhibitory activities.

Nine undescribed monoterpene indole alkaloids, rauvomitorine A-I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kα radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 µM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors.