Taburnaemines A-I, Cytotoxic Vobasinyl-Iboga-Type Bisindole Alkaloids from Tabernaemontana corymbosa

  • J Nat Prod. 2018 Mar 23;81(3):562-571. doi: 10.1021/acs.jnatprod.7b00949.
Yu Zhang  1 ,  Yu-Xi Yuan  1 ,  Masuo Goto  2 ,  Ling-Li Guo  1 ,  Xiao-Nian Li  1 ,  Susan L Morris-Natschke  2 ,  Kuo-Hsiung Lee  2  3 ,  Xiao-Jiang Hao  1
Affiliations
  • 1. State Key Laboratory of Phytochemistry and Plant Resources in West China , Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201 , Yunnan , People's Republic of China.
  • 2. Natural Product Research Laboratories, UNC Eshelman School of Pharmacy , University of North Carolina , Chapel Hill , North Carolina 27599-7568 , United States.
  • 3. Chinese Medicine Research and Development Center , China Medical University and Hospital , 2 Yuh-Der Road , Taichung , 40447 , Taiwan.
PMID: 29319316 DOI: 10.1021/acs.jnatprod.7b00949
Abstract

Nineteen vobasinyl-ibogan-type bisindole Alkaloids, including nine new compounds, taburnaemines A-I (1-9), were isolated from the twigs and leaves of Tabernaemontana corymbosa. The structures and absolute configurations of the new Alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids 1-5 contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while 6 has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid 1 and the known alkaloid tabernaecorymbosine A (10) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole Alkaloids, except 2 and 16'-decarbomethoxytabernaecorymbosine A (14), showed antiproliferative activity (IC50 2.6-9.8 μM) against several human Cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure-activity relationship correlations are also discussed.