Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Curr Pharm Des. 2024 Nov 5. doi: 10.2174/0113816128337881241016064641. Online 
ahead of print.

Design, Synthesis, and Molecular Docking of Quinazolines Bearing Caffeoyl Moiety 
for Targeting of PGK1/PKM2/STAT3 Signaling Pathway in the Human Breast Cancer.

Borik RM(1), Hussein MA(2).

Author information:
(1)Department of Physical Sciences, Chemistry Division, College of Science, 
Jazan University, P.O. Box. 114, Jazan 45142, KSA.
(2)Biotechnology Department, Faculty of Applied Health Science Technology, 
October 6 University, Giza 28125, Egypt.

BACKGROUND: PGK1 and PKM2 are glycolytic enzymes, and their expression is 
upregulated in cancer cells. STAT3 is a transcription factor implicated in 
breast cancer progression and chemoresistance. Researchers worldwide continue to 
explore how targeting genes might lead to more effective anti-breast cancer 
therapies. The present study aims to synthesize quinazolines containing caffeoyl 
moiety for developing innovative anticancer agents against the human breast 
cancer cell line (MCF-7).
METHODS: A new quinazoline 2 was synthesized by reacting caffeic acid with 
5-amino-phenylpyrazole carboxylate 1 in the presence of PCl3. Compound 2 reacted 
with NH2NH2.H2O to produce compound 3 through cyclo-condensation. Apoptosis and 
necrosis as well as inhibition activity compounds 2 and 3 against PGK1, and PKM2 
were evaluated. The effect of compounds 2 and 3 on the levels of GSH, GR, SOD, 
GPx, CAT, MDA, Bax, Bcl-2, caspase-3, P53 and VEGF levels as well as PGK1, PKM2 
and STAT3 gene expression were estimated in MCF-7 tumor cells.
RESULTS: The viability of MCF-7 cells was reduced to 22.42% and 45.86% after 
incubation with compounds 2 and 3 for 48 hours, respectively. The IC50 values 
for compounds 2 and 3 are 62.05 μg/mL and 16.73 μg/mL. Furthermore, compound 3 
exhibited more significant apoptosis and necrosis than compound 2. IC50 values 
of compound 2 against PGK1, and PKM2 at interval concentration equals 1.04, and 
0.32 μM/mL, respectively, after 210 minutes of incubation. Moreover, compound 3 
were revealed strong inhibition of PGK1, and PKM2 with IC50 values equals 0.55 
and 0.21 μg/mL, respectively after 210 minutes of incubation. Our results proved 
that the incubation of compounds 2 and 3 with MCF-7 cells increased the levels 
of apoptotic proteins, elevated MDA, Bax, caspase-3 and P53 levels, depleted 
GSH, GR, SOD, GPx, CAT, Bcl-2 levels and downregulated the levels of STAT3, 
PGK1, and PKM2 gene expression significantly. Our In-silico results proved that 
compound 2 showed a stronger estimated binding affinity with a ΔG of -7.2, -7.5, 
and - 7.9 kcal/mol., respectively towards PGK1, PKM2 and STAT3 proteins. Also, 
compound 3 exhibits a strong binding affinity with ΔG of -7.9, -8.5, and - 8.7 
kcal/mol., towards PGK1, PKM2 and STAT3 proteins.
CONCLUSION: The results show that compounds 2 and 3 induce apoptotic activity by 
blocking the PGK1- PKM2-STAT3 signaling pathway. The present investigation opens 
exciting possibilities for developing innovative new anticancer quinazolines 
bearing caffeoyl moiety.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0113816128337881241016064641
PMID: 39506445


2. Biosens Bioelectron. 2024 Nov 1;268:116904. doi: 10.1016/j.bios.2024.116904. 
Online ahead of print.

Designing a whole-cell biosensor applicable for 
S-adenosyl-l-methionine-dependent methyltransferases.

Zhen Z(1), Xiang L(2), Li S(1), Li H(1), Lei Y(1), Chen W(2), Jin JM(3), Liang 
C(4), Tang SY(5).

Author information:
(1)Department of Microbial Physiological & Metabolic Engineering, State Key 
Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of 
Sciences, 100101, Beijing, China; University of Chinese Academy of Sciences, 
100049, Beijing, China.
(2)Department of Microbial Physiological & Metabolic Engineering, State Key 
Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of 
Sciences, 100101, Beijing, China.
(3)Beijing Key Laboratory of Plant Resources Research and Development, Beijing 
Technology and Business University, 100048, Beijing, China. Electronic address: 
jinjianming@btbu.edu.cn.
(4)Department of Microbial Physiological & Metabolic Engineering, State Key 
Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of 
Sciences, 100101, Beijing, China. Electronic address: laraineliang@163.com.
(5)Department of Microbial Physiological & Metabolic Engineering, State Key 
Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of 
Sciences, 100101, Beijing, China. Electronic address: tangsy@im.ac.cn.

This study was undertaken to develop a high-throughput screening strategy using 
a whole-cell biosensor to enhance methyl-group transfer, a rate-limiting step 
influenced by intracellular methyl donor availability and methyltransferase 
efficiency. An l-homocysteine biosensor was designed based on regulatory protein 
MetR from Escherichia coli, which rapidly reported intracellular l-homocysteine 
accumulation resulted from S-adenosyl-l-homocysteine (SAH) formation after 
methyl-group transfer. Using S-adenosyl-l-methionine (SAM) as a methyl donor, 
this biosensor was applied to caffeic acid 3-O-methyltransferase derived from 
Arabidopsis thaliana (AtComT). After several rounds of directed evolution, the 
modified enzyme achieved a 13.8-fold improvement when converting caffeic acid to 
ferulic acid. The best mutant exhibited a 5.4-fold improvement in catalytic 
efficiency. Characterization of beneficial mutants showed that improved 
O-methyltransferase dimerization greatly contributed to enzyme activity. This 
finding was verified when we switched and compared the N-termini involved in 
dimerization across different sources. Finally, with tyrosine as a substrate, 
the evolved AtComT mutant greatly improved ferulic acid biosynthesis, yielding 
3448 mg L-1 with a conversion rate of 88.8%. These results have important 
implications for high-efficiency O-methyltransferase design, which will greatly 
benefit the biosynthesis of a wide range of natural products. In addition, the 
l-homocysteine biosensor has the potential for widespread applications in 
evaluating the efficiency of SAM-based methyl transfer.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.bios.2024.116904
PMID: 39504884

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.


3. Biophys Chem. 2023 Oct 20;304:107125. doi: 10.1016/j.bpc.2023.107125. Online 
ahead of print.

A combination of structure-based virtual screening and experimental strategies 
to identify the potency of caffeic acid ester derivatives as SARS-CoV-2 3CL(pro) 
inhibitor from an in-house database.

Pojtanadithee P(1), Isswanich K(2), Buaban K(3), Chamni S(3), Wilasluck P(4), 
Deetanya P(4), Wangkanont K(4), Langer T(5), Wolschann P(6), Sanachai K(7), 
Rungrotmongkol T(8).

Author information:
(1)Program in Bioinformatics and Computational Biology, Graduate School, 
Chulalongkorn University, Bangkok 10330, Thailand.
(2)Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical 
Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Department of 
Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, 
Chulalongkorn University, Bangkok 10330, Thailand; Natural Products and 
Nanoparticles Research Unit (NP2), Faculty of Pharmaceutical Sciences, 
Chulalongkorn University, Bangkok 10330, Thailand.
(3)Department of Pharmacognosy and Pharmaceutical Botany, Faculty of 
Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; 
Natural Products and Nanoparticles Research Unit (NP2), Faculty of 
Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
(4)Center of Excellence for Molecular Biology and Genomics of Shrimp, Department 
of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, 
Thailand; Center of Excellence for Molecular Crop, Department of Biochemistry, 
Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
(5)Department of Pharmaceutical Chemistry, Faculty of Chemistry, University of 
Vienna, Vienna 1090, Austria.
(6)Institute of Theoretical Chemistry, Vienna 1090, Austria.
(7)Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon 
Kaen 40002, Thailand. Electronic address: kamosa@kku.ac.th.
(8)Program in Bioinformatics and Computational Biology, Graduate School, 
Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence in 
Structural and Computational Biology, Department of Biochemistry, Faculty of 
Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: 
thanyada.r@chula.ac.th.

Drug development requires significant time and resources, and computer-aided 
drug discovery techniques that integrate chemical and biological spaces offer 
valuable tools for the process. This study focused on the field of COVID-19 
therapeutics and aimed to identify new active non-covalent inhibitors for 
3CLpro, a key protein target. By combining in silico and in vitro approaches, an 
in-house database was utilized to identify potential inhibitors. The 
drug-likeness criteria were considered to pre-filter 553 compounds from 12 
groups of natural products. Using structure-based virtual screening, 296 
compounds were identified that matched the chemical features of SARS-CoV-2 
3CLpro peptidomimetic inhibitor pharmacophore models. Subsequent molecular 
docking resulted in 43 hits with high binding affinities. Among the hits, 
caffeic acid analogs showed significant interactions with the 3CLpro active 
site, indicating their potential as promising candidates. To further evaluate 
their efficacy, enzyme-based assays were conducted, revealing that two ester 
derivatives of caffeic acid (4k and 4l) exhibited more than a 30% reduction in 
3CLpro activity. Overall, these findings suggest that the screening approach 
employed in this study holds promise for the discovery of novel anti-SARS-CoV-2 
therapeutics. Furthermore, the methodology could be extended for optimization or 
retrospective evaluation to enhance molecular targeting and antiviral efficacy 
of potential drug candidates.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.bpc.2023.107125
PMID: 39491914

Conflict of interest statement: Declaration of Competing Interest The authors 
have no conflicts of interest to declare.


4. RSC Adv. 2024 Oct 30;14(47):34756-34768. doi: 10.1039/d4ra05114a. eCollection 
2024 Oct 29.

Enhancement of antibacterial activity in electrospun fibrous membranes based on 
quaternized chitosan with caffeic acid and berberine chloride for wound dressing 
applications.

Chiu PH(1), Wu ZY(2), Hsu CC(1), Chang YC(2), Huang CM(1), Hu CT(1), Lin CM(1), 
Chang SC(2), Hsieh HJ(1), Dai CA(1).

Author information:
(1)Department of Chemical Engineering, National Taiwan University Taipei 10617 
Taiwan hjhsieh@ntu.edu.tw polymer@ntu.edu.tw.
(2)Graduate Institute of Microbiology, College of Medicine, National Taiwan 
University Taipei 10051 Taiwan.

Electrospun nanofibers made from chitosan are promising materials for surgical 
wound dressings due to their non-toxicity and biocompatibility. However, the 
antibacterial activity of chitosan is limited by its poor water solubility under 
physiological conditions. This study addresses this issue by producing 
electrospun nanofibers mainly from natural compounds, including chitosan and 
quaternized chitosan, which enhance both its solubility for electrospinning and 
the antibacterial activity of the resulting electrospun nanofibers. 
Additionally, antimicrobial agents like caffeic acid or berberine chloride were 
incorporated. The glutaraldehyde-treated nanofibers showed improved mechanical 
properties, with an average tensile strength exceeding 2.7 MPa, comparable to 
other chitosan-based wound dressings. They also demonstrated enhanced water 
stability, retaining over 50% of their original weight after one week in 
phosphate-buffered saline (PBS) at 37 °C. The morphology and performance of 
these nanofibers were thoroughly examined and discussed. Furthermore, these 
membranes displayed rapid drug release, indicating potential for inhibiting 
bacterial growth. Antibacterial assays revealed that S2-CX nanofibers containing 
caffeic acid were most effective against E. coli and S. aureus, reducing their 
survival rates to nearly 0%. Similarly, berberine chloride-containing S4-BX 
nanofibers reduced the survival rates of E. coli and S. aureus to 19.82% and 0%, 
respectively. These findings suggest that electrospun membranes incorporating 
chitosan and caffeic acid hold significant potential for use in antibacterial 
wound dressings and drug delivery applications.

This journal is © The Royal Society of Chemistry.

DOI: 10.1039/d4ra05114a
PMCID: PMC11526035
PMID: 39483382

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


5. Int J Biol Macromol. 2024 Oct 30:137108. doi: 10.1016/j.ijbiomac.2024.137108. 
Online ahead of print.

Biomimetic poly(thioctic acid)-based bioadhesive hydrogels for wet adhesion, 
expeditious hemostasis and enhanced wound healing.

Wang C(1), Yu F(1), Yuan Y(1), Zhao Z(2), Zhang L(3).

Author information:
(1)Sanya Science and Education Innovation Park, Wuhan University of Technology, 
Sanya 572000, China.
(2)Sanya Science and Education Innovation Park, Wuhan University of Technology, 
Sanya 572000, China; State Key Laboratory of Advanced Technology for Materials 
Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China. 
Electronic address: zhengzhao@whut.edu.cn.
(3)Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of 
Wuhan University, Wuhan 430070, China. Electronic address: llzhang@whu.edu.cn.

The bioadhesive hydrogels have been viewed as promising substitutes for surgical 
sutures in wound closure. However, current bioadhesives face challenges such as 
weak wet adhesion and hemostatic performance, which hinder their wider clinical 
application. In this study, a novel poly(thioctic acid)Li+/caffeic acid-grafted 
sericin (CAS) (PTALi-CAS) supramolecular hydrogel was prepared using facile 
one-pot method. Among the PTALi-CAS hydrogels with varying CAS content, the 
PTALi-7%CAS hydrogels exhibited the highest adhesion strength (32.02 ± 2.28 kPa) 
and could adhere on surfaces of various organs in moist environments. It is 
noteworthy that the microstructure of the PTALi-7%CAS hydrogels after stretching 
closely resemble those of mussel byssal adhesion proteins. Additionally, the 
PTALi-7%CAS hydrogels exhibited rapid hemostatic properties in rat hemorrhage 
models and significantly accelerated the wound healing in rat skin incision 
experiments. Therefore, this study proposes a promising approach for developing 
a versatile hydrogel to aid in healing traumatic wounds.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.ijbiomac.2024.137108
PMID: 39486699

Conflict of interest statement: Declaration of competing interest All authors 
declare no conflict of interest in this manuscript.