Flabellipparicine, a Flabelliformide-Apparicine-Type Bisindole Alkaloid from Tabernaemontana divaricata

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2018-09, Vol.81 (9), p.1976-1983
• Main Authors: Cai, You-Sheng, Sarotti, Ariel M, Zhou, Ting-Lan, Huang, Rong, Qiu, Guofu, Tian, Congkui, Miao, Ze-Hong, Mándi, Attila, Kurtán, Tibor, Cao, Shugeng, Yang, Sheng-Ping
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Cell Line, Tumor; Humans; Indole Alkaloids - chemistry; Indole Alkaloids - isolation & purification; Indole Alkaloids - pharmacology; Magnetic Resonance Spectroscopy; Monoterpenes - isolation & purification; Monoterpenes - pharmacology; Plant Stems - chemistry; Tabernaemontana - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.8b00191

Four new monoterpenoid bisindole alkaloids, flabellipparicine (1), 19,20-dihydrovobparicine (2), 10′-demethoxy-19,20-dihydrovobatensine D (3), and 3′-(2-oxopropyl)­ervahanine A (4), and 10 known monoterpenoid indole alkaloids were isolated from the stems of Tabernaemontana divaricata. All structures were elucidated based on spectroscopic methods, and the absolute configuration of 1 was established using conformational analysis and TDDFT-ECD calculation of selected stereoisomers. Compound 1 represents the first flabelliformide-apparicine-type bisindole alkaloid, in which the flabelliformide-like unit connects to the apparicine-like unit with a C-3–C-22′ bond and an N-1–C-16′ bond to form an uncommon five-membered ring between the two monomers. All alkaloids were evaluated for their cytotoxicity against two human cancer cell lines, MCF-7 and A-549. Compounds 2, 4, and 14 exhibited cytotoxicity against MCF-7 and A-549 with IC50 values in the range of 2 nM to 8 μM.