Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Int J Biol Macromol. 2024 Oct 28:136987. doi: 10.1016/j.ijbiomac.2024.136987. 
Online ahead of print.

A "pseudo" fluorescence indicator displacement assay based on "light-up" 
sanguinarine for identifying small ligands targeting HIV-1 RRE RNA.

Qi L(1), Gao Y(2), Zhang C(2), Chen J(2), Gong P(2), Liu Q(2).

Author information:
(1)Department of Pharmacy, School of Biomedical and Pharmaceutical Sciences, 
Shaanxi University of Science & Technology, Xi'an 710021, China. Electronic 
address: liangqi0712@126.com.
(2)Department of Pharmacy, School of Biomedical and Pharmaceutical Sciences, 
Shaanxi University of Science & Technology, Xi'an 710021, China.

Developing effective methods to identify drugs that can target HIV-1 Rev. 
response element (RRE) RNA and block the interaction between Rev. and RRE has 
practical significance in the treatment of AIDS. Fluorescence indicator 
displacement (FID) assay was commonly employed to identify small ligands binding 
to RNA. In this study, the non-fluorescent sanguinarine (Sang) was used as a 
novel "pseudo" fluorescence indicator to identify small ligands targeting RRE 
through its fluorescence "light-up", assisted by β-cyclodextrin (β-CD) or 
nano-SiO2. The fluorescence enhancement effect of β-CD or nano-SiO2 on Sang was 
initially examined. Subsequently, the Sang-RRE interaction was investigated and 
validated using circular dichroism, and the binding constants and binding sites 
of Sang to RRE were obtained; the competition between Sang and Rev. was explored 
and confirmed through molecular docking. Finally, the experimental parameters of 
the "pseudo" FID assay including reaction time, along with β-CD and nano-SiO2 
concentrations, were optimized using a well-known Rev. inhibitor (neomycin). 
Under the optimized experimental conditions, the evaluation of three positive 
inhibitors and one negative control was performed. These findings presented a 
novel approach for identifying small ligands targeting HIV-1 RRE RNA using a 
non-fluorescent ligand in the FID assay and established a promising screening 
platform.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.ijbiomac.2024.136987
PMID: 39476899

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


2. J Biomol Struct Dyn. 2024 Oct 21:1-18. doi: 10.1080/07391102.2024.2417226. 
Online ahead of print.

Molecular docking, network pharmacology, and QSAR modelling studies of 
benzo[c]phenanthridines - novel antileishmaniasis agents.

Kikaawa D(1), Vadivel E(1).

Author information:
(1)Chemistry Department, Dnyanprassarak Mandal's College and Research Center, 
Assagao - Bardez, Goa, India.

Leishmaniasis treatment primarily relies on chemotherapy due to lack of 
vaccines. However, the low efficacy, parasite resistance, and toxicity 
associated with existing drugs necessitate the development of effective and 
safer therapies. Fuchino et al. reported promising leishmanicidal activity in a 
series of benzo[c]phenanthridines against L. major promastigotes. To progress 
these compounds towards drug development, it is crucial to understand their 
molecular targets, mechanisms of action, binding interactions, and structural 
requirements. In this research, molecular docking, network pharmacology, 
2D-QSAR, and 3D-QSAR CoMFA studies were performed on 30 benzo[c]phenanthridines. 
Docking analysis showed that all molecules had a strong binding affinity to L. 
major-nucleoside diphosphate kinase (NDPK) compared to the other targets. 
10-isopropoxy sanguinarine had the highest binding affinity (-10.6 kcal/mol) and 
formed ionic and hydrophobic interactions. Network pharmacology analysis of the 
most active compounds identified serine/threonine-protein kinase Mtor as a 
potential antileishmaniasis target in humans for benzo[c]phenanthridines. This 
was confirmed with high-affinity scores > -7.0 kcal/mol for all the compounds 
docked. GO and KEGG pathway enrichment identified Reg. of fatty acid oxidation 
(BP), TORC1 complex (CC), RNA polymerase III type 1 promoter sequence-specific 
DNA binding (MF), and Acute myeloid leukemia (KEGG pathway) to be highly 
enriched with the hub genes. Both 2D and 3D-QSAR CoMFA models satisfied the 
internal and external validation tests as follows: 2D-QSAR: R2Train = 0.9040, 
Q2cv = 0.8648, R2adj = 0.8838, and R2Test = 0.8740; and 3D-QSAR: r2 = 0.998, q2 
= 0.526, and SDEP = 0.856. The molecules can be practically evaluated as 
superior antileishmaniasis agents.

DOI: 10.1080/07391102.2024.2417226
PMID: 39429050


3. Nat Commun. 2024 Oct 9;15(1):8759. doi: 10.1038/s41467-024-53045-3.

De novo production of protoberberine and benzophenanthridine alkaloids through 
metabolic engineering of yeast.

Jiao X(1), Fu X(1), Li Q(2), Bu J(2), Liu X(2), Savolainen O(1)(3), Huang L(4), 
Guo J(5), Nielsen J(6)(7), Chen Y(8).

Author information:
(1)Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, 
SE-412 96, Gothenburg, Sweden.
(2)State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di 
Herbs, National Resource Center for Chinese Materia Medica, China Academy of 
Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China.
(3)Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, 
Kemivägen 10, SE-412 96, Gothenburg, Sweden.
(4)State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di 
Herbs, National Resource Center for Chinese Materia Medica, China Academy of 
Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China. 
huangluqi01@126.com.
(5)State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di 
Herbs, National Resource Center for Chinese Materia Medica, China Academy of 
Chinese Medical Sciences, 16 Neinanxiaojie, Dongcheng district, Beijing, China. 
guojuanzy@163.com.
(6)Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, 
SE-412 96, Gothenburg, Sweden. nielsenj@chalmers.se.
(7)BioInnovation Institute, DK-2200, Copenhagen N, Denmark. 
nielsenj@chalmers.se.
(8)Department of Life Sciences, Chalmers University of Technology, Kemivägen 10, 
SE-412 96, Gothenburg, Sweden. yunc@chalmers.se.

Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups 
of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of 
plant-specialized natural metabolites with many pharmacological properties. 
Microbial biosynthesis has been allowed for accessibility and scalable 
production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de 
novo produce a series of protoberberines and BZDAs, including palmatine, 
berberine, chelerythrine, sanguinarine and chelirubine. An ER 
compartmentalization strategy is developed to improve vacuole protein berberine 
bridge enzyme (BBE) activity, resulting in >200% increase on the production of 
the key intermediate (S)-scoulerine. Another promiscuous vacuole protein 
dihydrobenzophenanthridine oxidase (DBOX) has been identified to catalyze 
two-electron oxidation on various tetrahydroprotoberberines at N7-C8 position 
and dihydrobenzophenanthridine alkaloids. Furthermore, cytosolically expressed 
DBOX can alleviate the limitation on BBE. This study highlights the potential of 
microbial cell factories for the biosynthesis of a diverse group of BIAs through 
engineering of heterologous plant enzymes.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-53045-3
PMCID: PMC11464499
PMID: 39384562 [Indexed for MEDLINE]

Conflict of interest statement: Y.C. and X.J. are inventors of pending patent 
applications (PCT/071270 and PCT/071276) arising from work on strategies for 
improved alkaloids production. Other authors declare no competing interests.


4. Chem Biodivers. 2024 Oct 4:e202402052. doi: 10.1002/cbdv.202402052. Online
ahead  of print.

Comprehensive Computational Screening and Analysis of Natural Compounds Reveals 
Promising Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy.

Alam P(1), Sharma P(2), Arshad MF(3).

Author information:
(1)King Saud University College of Pharmacy, Department of Pharmacognosy, 
College of Pharmacy, King Saud University, 11451, Riyadh, SAUDI ARABIA.
(2)All India Institute of Medical Sciences, Department of Biophysics, Sri 
Aurobindo Marg, New Delhi, INDIA.
(3)Isthmus Research and Publishing House, Department of Research and Scientific 
Communications, Mehrauli Badarpur road, New Delhi, INDIA.

Breast cancer remains a leading cause of death among women, with estrogen 
receptor alpha (ERα) overexpression playing a pivotal role in tumor growth and 
progression. This study aimed to identify novel ERα inhibitors from a library of 
561 natural compounds using computational techniques, including virtual 
screening, molecular docking, and molecular dynamics simulations. Four promising 
candidates-Protopine, Sanguinarine, Pseudocoptisine, and Stylopine-were selected 
based on their high binding affinities and interactions with key ERα residues. 
Molecular dynamics simulations conducted over 500 nanoseconds revealed that 
Protopine and Sanguinarine exhibited more excellent stability with minimal 
fluctuations, suggesting strong and stable binding. In contrast, Pseudocoptisine 
and Stylopine showed higher flexibility, indicating less stable interactions. 
Binding free energy calculations further supported the potential of Protopine 
and Sanguinarine as ERα inhibitors, though their binding strength was slightly 
lower than that of the reference compound. These findings highlight Protopine 
and Sanguinarine as leading candidates for further investigation, and in vitro 
and in vivo studies are recommended to evaluate their therapeutic potential in 
breast cancer treatment.

© 2024 Wiley‐VCH GmbH.

DOI: 10.1002/cbdv.202402052
PMID: 39363725


5. Bioorg Chem. 2024 Sep 24;153:107842. doi: 10.1016/j.bioorg.2024.107842. Online
 ahead of print.

Identification of sanguinarine as c-MYC transcription inhibitor through 
enhancing the G-quadruplex-NM23-H2 interactions.

Zhong LT(1), Yuan JM(2), Fu WL(1), Zhang ZL(1), Li X(3), Ou TM(1), Tan JH(4), 
Huang ZS(1), Chen SB(5).

Author information:
(1)School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
China.
(2)Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of 
Chemistry and Materials, Nanning Normal University, Nanning 530001, China.
(3)Department of Nephrology, Nanfang Hospital, Southern Medical University, No. 
1838, Guangzhou Avenue North, Baiyun District, Guangzhou, Guangdong, China.
(4)School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
China. Electronic address: tanjiah@mail.sysu.edu.cn.
(5)School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
China. Electronic address: chenshb8@mail.sysu.edu.cn.

c-MYC is a proto-oncogene ubiquitously overexpressed in various cancers. The 
formation of G-quadruplex (G4) structures within the c-MYC promoter region can 
regulate its transcription by interfering with protein binding. Consequently, 
small molecules targeting c-MYC G4 have emerged as promising anticancer agents. 
Herein, we report that sanguinarine (SG) and its analogs exhibit a high affinity 
for c-MYC G4 and potently modulate G4-protein interactions within a natural 
product library. Notably, SG uniquely enhances NM23-H2 binding to c-MYC G4, both 
in vitro and in cellular contexts, leading to c-MYC transcriptional repression 
and subsequent inhibition of cancer cell growth in an NM23-H2-dependent manner. 
Mechanistic studies and molecular modeling suggest that SG binds to the c-MYC 
G4/NM23-H2 interface, acting as an orthosteric stabilizer of the DNA-protein 
complex and preventing c-MYC transcription. Our findings identify SG as a potent 
c-MYC transcription inhibitor and provide a novel strategy for developing 
G4-targeting anticancer therapeutics through modulation of G4-protein 
interactions.

Copyright © 2024 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.bioorg.2024.107842
PMID: 39342890

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.