Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Agric Food Chem. 2024 Jul 10;72(27):15293-15300. doi: 
10.1021/acs.jafc.4c04228. Epub 2024 Jun 28.

Multienzymatic Cascade for Synthesis of Hydroxytyrosol via Two-Stage 
Biocatalysis.

Liu WK(1)(2), Su BM(1)(2), Xu XQ(1)(2), Xu L(1)(2), Lin J(1)(2).

Author information:
(1)College of Biological Science and Engineering, Fuzhou University, Fuzhou 
350108, China.
(2)Institute of Enzyme Catalysis and Synthetic Biotechnology, Fuzhou University, 
Fuzhou 350108, China.

Hydroxytyrosol, a naturally occurring compound with antioxidant and antiviral 
activity, is widely applied in the cosmetic, food, and nutraceutical industries. 
The development of a biocatalytic approach for producing hydroxytyrosol from 
simple and readily accessible substrates remains a challenge. Here, we designed 
and implemented an effective biocatalytic cascade to obtain hydroxytyrosol from 
3,4-dihydroxybenzaldehyde and l-threonine via a four-step enzymatic cascade 
composed of seven enzymes. To prevent cross-reactions and protein expression 
burden caused by multiple enzymes expressed in a single cell, the designed 
enzymatic cascade was divided into two modules and catalyzed in a stepwise 
manner. The first module (FM) assisted the assembly of 3,4-dihydroxybenzaldehyde 
and l-threonine into (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic 
acid, and the second module (SM) entailed converting 
(2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid into 
hydroxytyrosol. Each module was cloned into Escherichia coli BL21 (DE3) and 
engineered in parallel by fine-tuning enzyme expression, resulting in two 
engineered whole-cell catalyst modules, BL21(FM01) and BL21(SM13), capable of 
converting 30 mM 3,4-dihydroxybenzaldehyde to 28.7 mM hydroxytyrosol with a high 
space-time yield (0.88 g/L/h). To summarize, the current study proposes a simple 
and effective approach for biosynthesizing hydroxytyrosol from low-cost 
substrates and thus has great potential for industrial applications.

DOI: 10.1021/acs.jafc.4c04228
PMID: 38940657 [Indexed for MEDLINE]


2. J Chromatogr Sci. 2024 Nov 1;62(9):815-820. doi: 10.1093/chromsci/bmae009.

Pharmacokinetic Analysis of Two N-Substituted Rosmarinic Acid Analogs in Rat 
Plasma by Liquid Chromatography-Tandem Mass Spectrometry.

Fu S(1), Zhang Q(2), Zhang S(2), Jiang W(1), Jiang M(2).

Author information:
(1)School of Pharmaceutical, Guangxi Medical University, Nanning 530021, China.
(2)Guangxi University of Chinese Medicine, Nanning 530001, China.

This study reports the development of an effective high-performance liquid 
chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the 
quantification of two analogs of rosmarinic acid (RA) in rat plasma, namely 
methyl 
(E)-2-(3-(3,4-difluorophenyl)acrylamido)-3-(3,4-dihydroxyphenyl)propanoate (A11) 
and methyl 
(E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoate 
(A2). These analogs, featuring N atoms instead of O atoms, exhibit enhanced 
bioavailability and distinct pharmacological activities compared with RA. The 
HPLC separation was carried out on a C18 column (1.9 μm, 2.1 mm × 100 mm) 
coupled with a security guard C18 column (5 μm, 2.1 mm × 10 mm). A 
triple-quadrupole mass spectrometer equipped with an electrospray ionization ion 
source was utilized for ion generation. Pseudoephedrine hydrochloride was 
utilized as a standard, and a single-step protein precipitation method using 
isopropanol:ethyl acetate (v/v, 20:80) was employed for sample pretreatment. The 
developed method demonstrated excellent linearity over the concentration range 
of 5-750 ng/ml for both A11 and A2, with relative standard deviations of <15% 
and relative errors within 15% during daily course analysis. The method allowed 
for the unambiguous quantification and identification of A11 and A2 in vivo. The 
results of this study provide a meaningful foundation for evaluating the 
clinical applications of these analogs.

© The Author(s) 2024. Published by Oxford University Press. All rights reserved. 
For permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/chromsci/bmae009
PMID: 38520038 [Indexed for MEDLINE]


3. Rapid Commun Mass Spectrom. 2023 Sep 15;37(17):e9598. doi: 10.1002/rcm.9598.

Determination of rosmarinic acid and its N-substituted analog A1 in rat plasma 
using high-performance liquid chromatography-tandem mass spectrometry and its 
application in pharmacokinetics.

Fu S(1), Zhang Q(2), Zhang S(2), Jiang W(1), Jiang M(2).

Author information:
(1)Pharmaceutical College, Guangxi Medical University, Nanning, China.
(2)Guangxi University of Chinese Medicine, Nanning, China.

BACKGROUND: The aim of this study was to determine the concentration of 
rosmarinic acid (RA) and its analog 
(E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoic acid 
(A1) in rat plasma following oral administration. The significance of this study 
lies in the development of a rapid, sensitive, and alternative method using 
liquid chromatography-tandem mass spectrometry for the accurate quantification 
and identification of RA and A1 in vivo.
METHODS: Liquid chromatography-tandem mass spectrometry was employed to analyze 
RA and A1 in rat plasma. A C18 column (1.9 µm, 2.1 × 100 mm) with a C18 guard 
column (5 µm, 2.1 × 10 mm) and a triple-quadrupole mass spectrometer combined 
with an electrospray ionization source were utilized. Sample pretreatment 
involved a one-step protein precipitation using isopropanol:ethyl acetate 
(20:80, v/v) as the solvent. Pseudoephedrine hydrochloride served as a standard.
RESULTS: The developed method exhibited a linear relationship within the 
concentration ranges of 5-750 ng/ml for both RA and A1. Relative standard 
deviations in daily courses were less than 15%, and the relative errors recorded 
were within 15%. This is the first study to concentrate on determining A1 and RA 
in rat plasma through oral administration.
CONCLUSIONS: The liquid chromatography-tandem mass spectrometry method developed 
in this study offers a rapid, sensitive, and alternative approach for the 
accurate quantification and identification of RA and A1 in vivo. The findings 
serve as a significant foundation for evaluating the clinical applications of 
the medicine.

© 2023 John Wiley & Sons Ltd.

DOI: 10.1002/rcm.9598
PMID: 37580502 [Indexed for MEDLINE]


4. ChemMedChem. 2022 Dec 16;17(24):e202200400. doi: 10.1002/cmdc.202200400. Epub 
2022 Nov 9.

Prodrugs of the Archetypal Dynamin Inhibitor Bis-T-22.

Odell LR(1)(2), Robertson MJ(1)(3), Young KA(1), McGeachie AB(4), Quan A(4), 
Robinson PJ(4), McCluskey A(1).

Author information:
(1)The University of Newcastle, University Drive, Callaghan, NSW 2308, 
Australia.
(2)Present address: Department of Medicinal Chemistry, Uppsala University, Box 
574, 75123, Uppsala, Sweden.
(3)Present address: Chemistry, College of Science & Engineering, James Cook 
University, Townsville, QLD 4814, Australia.
(4)Cell Signalling Unit, Children's Medical Research Institute, The University 
of Sydney, 214 Hawkesbury Road, Westmead, NSW 2145, Australia.

The Bis-T series of compounds comprise some of the most potent inhibitors of 
dynamin GTPase activity yet reported, e. g., 
(2E,2'E)-N,N'-(propane-1,3-diyl)bis(2-cyano-3-(3,4-dihydroxyphenyl)acrylamide) 
(2), Bis-T-22. The catechol moieties are believed to limit cell permeability, 
rendering these compounds largely inactive in cells. To solve this problem, a 
prodrug strategy was envisaged and eight ester analogues were synthesised. The 
shortest and bulkiest esters (acetate and butyl/tert-butyl) were found to be 
insoluble under physiological conditions, whilst the remaining five were soluble 
and stable under these conditions. These five were analysed for plasma stability 
and half-lives ranged from ∼2.3 min (propionic ester 4), increasing with size 
and bulk, to greater than 24 hr (dimethyl carbamate 10). Similar profiles where 
observed with the rate of formation of Bis-T-22 with half-lives ranging from 
∼25 mins (propionic ester 4). Propionic ester 4 was chosen to undergo further 
testing and was found to inhibit endocytosis in a dose-dependent manner with 
IC50 ∼8 μM, suggesting this compound is able to effectively cross the cell 
membrane where it is rapidly hydrolysed to the desired Bis-T-22 parent compound.

© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.

DOI: 10.1002/cmdc.202200400
PMCID: PMC10947042
PMID: 36351775 [Indexed for MEDLINE]

Conflict of interest statement: We have a commercial agreement to supply dynamin 
inhibitors via Abcam UK


5. Pharmaceutics. 2022 Jan 4;14(1):115. doi: 10.3390/pharmaceutics14010115.

Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of 
Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family.

Merlani M(1), Scheibel DM(2), Barbakadze V(1), Gogilashvili L(1), Amiranashvili 
L(1), Geronikaki A(3), Catania V(4), Schillaci D(4), Gallo G(5), Gitsov 
I(2)(6)(7).

Author information:
(1)Kutateladze Institute of Pharmacochemistry, Tbilisi State Medical University, 
36 P.Sarajishvili Street, 0159 Tbilisi, Georgia.
(2)Department of Chemistry, College of Environmental Science and Forestry, State 
University of New York, 1 Forestry Drive, Syracuse, NY 13210, USA.
(3)School of Pharmacy, Aristotle University, 54124 Thessaloniki, Greece.
(4)Laboratory of Microbiology and Biologic Assays, Department of Biological, 
Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 32 
Via Archirafi, 90123 Palermo, Italy.
(5)Laboratory of Molecular Microbiology and Biotechnology, Department of 
Biological, Chemical and Pharmaceutical Sciences and Technologies, University of 
Palermo, Viale delle Scienze, ed. 16, 90128 Palermo, Italy.
(6)The Michael M. Szwarc Polymer Research Institute, Syracuse, NY 13210, USA.
(7)The BioInspired Institute, Syracuse University, Syracuse, NY 13210, USA.

This study reports the first enzymatic synthesis leading to several oligomer 
analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, 
extracted from plants of the Boraginaceae family has shown a wide spectrum of 
pharmacological properties, including antimicrobial activity. Enzymatic ring 
opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane 
(MDBPO) using lipase from Candida rugosa leads to formation of 
poly[2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane] (PMDBPO), with a degree 
of polymerization up to 5. Catalytic debenzylation of PMDBPO using H2 on Pd/C 
yields poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) without 
loss in molecular mass. Antibacterial assessment of natural polyethers from 
different species of Boraginaceae family Symhytum asperum, S. caucasicum,S. 
grandiflorum, Anchusa italica, Cynoglossum officinale, and synthetic polymers, 
poly[2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (PMDMPO) and PMDHPO, 
reveals that only the synthetic analogue produced in this study (PMDHPO) 
exhibits a promising antimicrobial activity against pathogenic strains S.aureus 
ATCC 25923 and E.coli ATCC 25922 the minimum inhibitory concentration (MIC) 
being 100 µg/mL.

DOI: 10.3390/pharmaceutics14010115
PMCID: PMC8779701
PMID: 35057011

Conflict of interest statement: The authors declare no conflict of interest. The 
funders had no role in the design of the study; in the collection, analyses, or 
interpretation of data; in the writing of the manuscript, or in the decision to 
publish the results.