Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Planta Med. 2021 Feb;87(1-02):136-147. doi: 10.1055/a-1315-2282. Epub 2020 Dec
 15.

Precursor-directed Biosynthesis in Tabernaemontana catharinensis as a New Avenue 
for Alzheimer's Disease-modifying Agents.

Musquiari B(1), Crevelin EJ(2), Bertoni BW(1)(3), França SC(1), Pereira 
AMS(1)(3), Castello ACD(4), Castillo-Ordoñez WO(5), Giuliatti S(6), Lopes AA(1).

Author information:
(1)Biotechnology Unit, University of Ribeirão Preto (UNAERP), Ribeirão Preto, 
SP, Brazil.
(2)Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, Universidade 
de São Paulo (USP), Ribeirão Preto, SP, Brazil.
(3)Botanic Garden of Medicinal Plant Ordem e Progresso (BOP), Jardinópolis, SP, 
Brazil.
(4)State University of Campinas (UNICAMP), Institute of Biology, Department of 
Botany, Campinas, SP, Brazil.
(5)Department of Biology, Faculty of Natural Sciences, Exacts and Education, 
University of Cauca, Popayán Colombia.
(6)Department of Genetics, Ribeirão Preto Medical School, University of São 
Paulo (USP), Ribeirão Preto, SP, Brazil.

Plants produce a high diversity of metabolites that can act as regulators of 
cholinergic dysfunction. Among plants, the potential of species of the genus 
Tabernaemontana to treat neurological disorders has been linked to iboga-type 
alkaloids that are biosynthesized by those species. In this context, 
precursor-directed biosynthesis approaches were carried out using T. 
catharinensis plantlets to achieve new-to-nature molecules as promising agents 
against Alzheimer's disease. Aerial parts of T. catharinensis, cultured in 
vitro, produced 7 unnatural alkaloids (5-fluoro-ibogamine, 
5-fluoro-voachalotine, 5-fluoro-12-methoxy-Nb-methyl-voachalotine, 
5-fluoro-isovoacangine, 5-fluoro-catharanthine, 
5-fluoro-19-(S)-hydroxy-ibogamine, and 5-fluoro-coronaridine), while root 
extracts showed the presence of the same unnatural iboga-type alkaloids and 2 
additional ones: 5-fluoro-voafinine and 5-fluoro-affinisine. Moreover, molecular 
docking approaches were carried out to evaluate the potential inhibition 
activity of T. catharinensis' natural and unnatural alkaloids against AChE and 
BChE enzymes. Fluorinated iboga alkaloids (5-fluoro-catharanthine, 
5-fluoro-voachalotine, 5-fluoro-affinisine, 5-fluoro-isovoacangine, 
5-fluoro-corinaridine) were more active than natural ones and controls against 
AchE, while 5-fluoro-19-(S)-hydroxy-ibogamine, 5-fluoro-catharanthine, 
5-fluoro-isovoacangine, and 5-fluoro-corinaridine showed better activity than 
natural ones and controls against BChE. Our findings showed that 
precursor-directed biosynthesis strategies generated "new-to-nature" alkaloids 
that are promising Alzheimer's disease drug candidates. Furthermore, the 
isotopic experiments also allowed us to elucidate the initial steps of the 
biosynthetic pathway for iboga-type alkaloids, which are derived from the MEP 
and shikimate pathways.

Thieme. All rights reserved.

DOI: 10.1055/a-1315-2282
PMID: 33321518 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no conflict 
of interest.


2. Molecules. 2019 Apr 3;24(7):1316. doi: 10.3390/molecules24071316.

Preparative Separation of Monoterpenoid Indole Alkaloid Epimers from Ervatamia 
yunnanensis Tsiang by pH-Zone-Refining Counter-Current Chromatography Combined 
with Preparative High-Performance Liquid Chromatography.

Zhou J(1), Du SY(2), Dong HJ(3), Fang L(4)(5), Feng JH(6).

Author information:
(1)School of Biological Science and Technology, University of Jinan, Jinan 
250022, China. zhoujie8761@163.com.
(2)Key laboratory of Natural Pharmaceutical Chemistry, Shandong University of 
Traditional Chinese Medicine, Jinan 250200, China. dsy_fine@163.com.
(3)Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis 
and Test Center, Qilu University of Technology (Shandong Academy of Sciences), 
Jinan 250014, China. donghongjing_2006@163.com.
(4)School of Biological Science and Technology, University of Jinan, Jinan 
250022, China. fleiv@163.com.
(5)Key laboratory of Natural Pharmaceutical Chemistry, Shandong University of 
Traditional Chinese Medicine, Jinan 250200, China. fleiv@163.com.
(6)Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis 
and Test Center, Qilu University of Technology (Shandong Academy of Sciences), 
Jinan 250014, China. fengjinhong520@163.com.

An effective method was developed for the preparative separation and 
purification of monoterpenoid indole alkaloid epimers from Ervatamia yunnanensis 
Tsiang using a combination of pH-zone-refining counter-current chromatography 
and preparative high-performance liquid chromatography. With this method, two 
pairs of MIA epimers including ervatamine (72 mg, 1), 20-epi-ervatamine (27 mg, 
4), dregamine (95 mg, 2), tabernaemontanine (129 mg, 3), along with two MIAs, 
apparicine (112 mg, 5) and isovoacangine (15 mg, 6), were successfully purified 
from 2.1 g crude extract of E. yunnanensis, each with a purity of over 95% as 
determined by HPLC. The structures of the MIAs were identified by ESI-MS, 1D, 
and 2D NMR.

DOI: 10.3390/molecules24071316
PMCID: PMC6480700
PMID: 30987224 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.


3. Zhongguo Zhong Yao Za Zhi. 2018 Apr;43(7):1471-1475. doi: 
10.19540/j.cnki.cjcmm.20180115.007.

[Studies on alkaloids from Ervatamia pandacaqui].

[Article in Chinese]

Zhang QH(1)(2), Ding Y(1)(2), Bai WX(1)(2), Zhang J(1)(2), Zhang XQ(1)(2), Ye 
WC(1)(2).

Author information:
(1)Institute of Traditional Chinese Medicine & Natural Products, College of 
Pharmacy, Ji'nan University, Guangzhou 510632, China.
(2)Guangdong Technology Research Center for Advanced Chinese Medicine, College 
of Pharmacy, Ji'nan University, Guangzhou 510632, China.

To inverstigate the alkaloids from the twigs and leaves of Ervatamia pandacaqui, 
eleven known alkaloids were isolated by silica gel, Sephadex LH-20, and ODS 
column chromatography, as well as RP-HPLC. Their structures were elucidated by 
UV, IR, MS, and NMR spectral data as coronaridine (1), 3-oxocoronaridine (2), 
19S-heyneanine (3), 19R-heyneanine (4), voacangine (5), 3-oxovoacangine (6), 
voacristine (7), 19-epi-voacristine (8), iso-voacangine (9), coronaridine 
7-hydroxyindolenine (10), and voacangine 7-hydroxyindolenine (11). Compounds 
1-11 were isolated from E. pandacaqui for the first time.

Copyright© by the Chinese Pharmaceutical Association.

DOI: 10.19540/j.cnki.cjcmm.20180115.007
PMID: 29728039 [Indexed for MEDLINE]

Conflict of interest statement: The authors of this article and the planning 
committee members and staff have no relevant financial relationships with 
commercial interests to disclose.


4. Bioorg Med Chem Lett. 2015 Sep 15;25(18):3937-40. doi: 
10.1016/j.bmcl.2015.07.036. Epub 2015 Jul 21.

Coronaridine, an iboga type alkaloid from Tabernaemontana divaricata, inhibits 
the Wnt signaling pathway by decreasing β-catenin mRNA expression.

Ohishi K(1), Toume K(1), Arai MA(1), Sadhu SK(2), Ahmed F(3), Ishibashi M(4).

Author information:
(1)Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, 
Chuo-ku, Chiba 260-8675, Japan.
(2)Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, 
Bangladesh.
(3)Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, 
Bangladesh.
(4)Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, 
Chuo-ku, Chiba 260-8675, Japan. Electronic address: mish@chiba-u.jp.

Four alkaloids, voacangine (1), isovoacangine (2), coronaridine (3), and 
coronaridine hydroxyindolenine (4), were isolated from the MeOH extract of 
Tabernaemontana divaricata aerial parts by activity-guided fractionation for Wnt 
signal inhibitory activity. Compounds 1-4 exhibited TCF/β-catenin inhibitory 
activities with IC50 values of 11.5, 6.0, 5.8, and 7.3 μM, respectively. Of 
these, coronaridine (3) decreased β-catenin levels in SW480 colon cancer cells, 
while this decrease in β-catenin was not suppressed by a co-treatment with 3 and 
MG132, a proteasome inhibitor. These results suggested that the decrease 
observed in β-catenin levels by coronaridine (3) did not depend on a proteasomal 
degradation process. On the other hand, the treatment of SW480 cells with 
coronaridine (3) caused a decrease in β-catenin mRNA levels. Thus, coronaridine 
(3) may inhibit the Wnt signaling pathway by decreasing the mRNA expression of 
β-catenin.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.bmcl.2015.07.036
PMID: 26231157 [Indexed for MEDLINE]


5. Planta Med. 1998 Mar;64(2):148-52. doi: 10.1055/s-2006-957393.

Leaf alkaloid contents of Tabernaemontana pachysiphon as influenced by 
endogenous and environmental factors in the natural habitat.

Höft M(1), Verpoorte R, Beck E.

Author information:
(1)Lehrstuhl Pflanzenphysiologie, Universität Bayreuth, Bayreuth, Germany.

Indole alkaloid contents were investigated in leaves of Tabernaemontana 
pachysiphon (Apocynaceae) trees in the natural habitat, Shimba Hills National 
Reserve, Kenya. The contents of the major alkaloids apparicine, tubotaiwine, 
tubotaiwine- N-oxide, and isovoacangine varied with site, leaf age, leaf growth 
form, position in the crown, and plant age. Alkaloid contents were highest in 
young leaves. Trees bearing aberrant small dwarf-leaves showed similar alkaloid 
patterns as young leaves from healthy trees. At single trees, the contents were 
found to increase from the top to the bottom of the crown. Tree age had little 
influence on leaf alkaloid contents. In even aged leaves of trees from different 
forest sites, alkaloid contents were highest at the site with highest soil 
cation exchange capacity (CEC) and base saturation.

DOI: 10.1055/s-2006-957393
PMID: 17253230