Indoline alkaloids from Tabernaemontana contorta with cancer chemopreventive activity

Joseph Thierry Ndongo; Joséphine Ngo Mbing; Michel Feussi Tala; Aymeric Monteillier; Dieudonné Emmanuel Pegnyemb; Muriel Cuendet; Hartmut Laatsch

doi:10.1016/j.phytochem.2017.09.013

Indoline alkaloids from Tabernaemontana contorta with cancer chemopreventive activity

Phytochemistry. 2017 Dec:144:189-196. doi: 10.1016/j.phytochem.2017.09.013. Epub 2017 Sep 23.

Authors

Joseph Thierry Ndongo¹, Joséphine Ngo Mbing², Michel Feussi Tala³, Aymeric Monteillier⁴, Dieudonné Emmanuel Pegnyemb², Muriel Cuendet⁴, Hartmut Laatsch⁵

Affiliations

¹ Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P. O. Box 47, Yaoundé, Cameroon; University of Goettingen, Institute of Organic and Biomolecular Chemistry, Tammannstrasse 2, D-37077 Goettingen, Germany. Electronic address: thierry.ndongo@ens.cm.
² Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon.
³ University of Goettingen, Institute of Organic and Biomolecular Chemistry, Tammannstrasse 2, D-37077 Goettingen, Germany.
⁴ Section des Sciences Pharmaceutiques, University of Geneva, University of Lausanne, Rue Michel-Servet 1, CH-1211 Genève 4, Switzerland.
⁵ University of Goettingen, Institute of Organic and Biomolecular Chemistry, Tammannstrasse 2, D-37077 Goettingen, Germany. Electronic address: hlaatsc@gwdg.de.

PMID: 28950224
DOI: 10.1016/j.phytochem.2017.09.013

Abstract

Two bisindoline alkaloids, contortarine A, 16-epi-pleiomutinine and a reaction product of pleiomutinine, namely N⁴-chloromethyl-pleiomutinine, were isolated from the roots of Tabernaemontana contorta Stapf. together with five known compounds: pleiomutinine, 1-carbomethoxy-β-carboline, strictosidine lactam, pleiocarpamine, and pleiocarpine. The structures and relative configuration of these alkaloids were determined by extensive 1D and 2D NMR, and MS measurements. The absolute configuration of these compounds was determined by comparison of experimental and calculated ECD spectra. Among the isolated compounds, contortarine A, 1-carbomethoxy-β-carboline and strictosidine lactam presented cancer chemopreventive properties through either quinone reductase (QR) induction with C_D values of 16.0 ± 2.5, 30.2 ± 6.1 and 23.1 ± 4.6 μM, respectively, while pleiomutinine and 16-epi-pleiomutinine displayed the inhibition of TNF-α induced NF-κB activity with IC₅₀ at 11.7 ± 2.6 and 3.4 ± 1.1 μM, respectively.

Keywords: 16-epi-pleiomutinine; Apocynaceae; Cancer chemopreventive properties; Contortarine A; ECD; N(4)-Chloromethyl-pleiomutinine; Tabernaemontana contorta.

MeSH terms

Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification*
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
HEK293 Cells
Humans
Indoles / chemistry
Indoles / isolation & purification
Indoles / pharmacology*
Molecular Structure
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
Neoplasms / pathology
Neoplasms / prevention & control*
Plant Roots / chemistry
Tabernaemontana / chemistry*

Substances

Alkaloids
Antineoplastic Agents, Phytogenic
Indoles
NF-kappa B
indoline