Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. RSC Adv. 2022 Apr 5;12(17):10204-10208. doi: 10.1039/d2ra01154a. eCollection 
2022 Mar 31.

The Reformatsky analogous reaction for the synthesis of novel β-thioxoesters via 
using aroyl isothiocyanates under solvent-free ball milling and conventional 
conditions.

Farag PS(1), Hemdan MM(1), Hassaballah AI(1).

Author information:
(1)Chemistry Department, Faculty of Science, Ain Shams University Abbassia 11566 
Cairo Egypt ayaibrahim@sci.asu.edu.eg.

The classical Reformatsky reaction, initially described in 1887, is considered 
one of the most useful ways of forming C-C bonds. The target of this work 
includes improving the Reformatsky reaction between aroyl isothiocyanates and 
α-haloesters using metallic zinc to form β-thioxoesters (3-11). In this 
procedure, a new metal-mediated carbon-carbon linkage is formed with the 
formation of an organozinc halide and decomposition due to the presence of 
dilute acid, affording a good yield of the desired product via conventional 
techniques and ball milling. The Reformatsky reaction requires no solvent and no 
inert gases.

This journal is © The Royal Society of Chemistry.

DOI: 10.1039/d2ra01154a
PMCID: PMC8982458
PMID: 35424970

Conflict of interest statement: The authors declare no competing financial 
interests.


2. Mol Neurobiol. 2021 Mar;58(3):1114-1127. doi: 10.1007/s12035-020-02174-z. Epub
 2020 Oct 23.

Prostaglandin A1 Decreases the Phosphorylation of Tau by Activating Protein 
Phosphatase 2A via a Michael Addition Mechanism at Cysteine 377.

Xu GB(#)(1)(2), Guan PP(#)(1), Wang P(3).

Author information:
(1)College of Life and Health Sciences, Northeastern University, No. 3-11. 
Wenhua Road, Shenyang, 110819, People's Republic of China.
(2)Liaoning Cheng Da Biotechnology Co., Ltd, Shenyang, 110179, People's Republic 
of China.
(3)College of Life and Health Sciences, Northeastern University, No. 3-11. 
Wenhua Road, Shenyang, 110819, People's Republic of China. 
wangpu@mail.neu.edu.cn.
(#)Contributed equally

Prostaglandin (PG) A1 is a metabolic product of cyclooxygenase 2 (COX-2) that is 
potentially involved in regulating the development and progression of 
Alzheimer's disease (AD). PGA1 is a cyclopentenone (cy) PG characterized by the 
presence of a chemically reactive α,β-unsaturated carbonyl. PGA1 is potentially 
involved in the regulation of multiple biological processes via Michael 
addition; however, the specific roles of PGA1 in AD remain unclear. TauP301S 
transgenic (Tg) mice were used as in vivo AD models, and neuroblastoma (N) 2a 
cells were used as an in vitro neuronal model. The PGA1-binding proteins were 
identified by HPLC-MS-MS after intracerebroventricular injection (i.c.v) of 
PGA1. Western blotting was used to determine tau phosphorylation in PGA1-treated 
Tg mice in the absence or in the presence of okadaic acid (OA), an inhibitor of 
protein phosphatase (PP) 2A. A combination of pull-down assay, 
immunoprecipitation, western blotting, and HPLC-MS-MS was used to determine that 
the PP2A scaffold subunit A alpha (PPP2R1A) is activated by the direct binding 
of PGA1 to cysteine 377. The effect of inhibiting tau hyperphosphorylation was 
tested in the Morris maze to determine the inhibitory effects of PGA1 on 
cognitive decline in tauP301S Tg mice. Incubation with N2a cells, pull-down 
assay, and mass spectrometry (MS) analysis revealed and indicated that PGA1 
binds to more than 1000 proteins; some of these proteins are associated with AD 
and especially with tauopathies. Moreover, short-term administration of PGA1 in 
tauP301S Tg mice significantly decreased tau phosphorylation at Thr181, Ser202, 
and Ser404 in a dose-dependent manner. This effect was caused by the activation 
of PPP2R1A in tauP301S Tg mice. Importantly, PGA1 can form a Michael adduct with 
cysteine 377 of PPP2R1A, which is critical for the enzymatic activity of PP2A. 
Long-term treatment of tauP301S Tg mice with PGA1 activated PP2A and 
significantly reduced tau phosphorylation resulting in improvements in cognitive 
decline in tauP301S Tg mice. Our data provided new insight into the mechanisms 
of the ameliorating effects of PGA1 on cognitive decline in tauP301S Tg mice by 
activating PP2A via a mechanism involving the formation of a Michael adduct with 
cysteine 377 of PPP2R1A.

DOI: 10.1007/s12035-020-02174-z
PMID: 33095414 [Indexed for MEDLINE]


3. PLoS One. 2016 Apr 29;11(4):e0154645. doi: 10.1371/journal.pone.0154645. 
eCollection 2016.

PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas.

Kartha VK(1)(2), Stawski L(3), Han R(3), Haines P(3), Gallagher G(4), Noonan 
V(4), Kukuruzinska M(5), Monti S(2), Trojanowska M(3).

Author information:
(1)Bioinformatics Program, Boston University, Boston, Massachusetts, United 
States of America.
(2)Division of Computational Biomedicine, Boston University School of Medicine, 
Boston, Massachusetts, United States of America.
(3)Arthritis Center, Boston University School of Medicine, Boston, 
Massachusetts, United States of America.
(4)Division of Oral Pathology, Boston University School of Dental Medicine, 
Boston, Massachusetts, United States of America.
(5)Department of Molecular and Cell Biology, Boston University School of Dental 
Medicine, Boston, Massachusetts, United States of America.

Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor 
stroma and play an important role in tumor growth and invasion. The presence of 
CAFs is a strong predictor of poor prognosis of head and neck squamous cell 
carcinoma. Despite significant progress in determining the role of CAFs in tumor 
progression, the mechanisms contributing to their activation remain poorly 
characterized, in part due to fibroblast heterogeneity and the scarcity of 
reliable fibroblast surface markers. To search for such markers in oral squamous 
cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data 
derived from the cancer genome atlas (TCGA). Specifically, our strategy allowed 
for an unbiased identification of genes whose expression was closely associated 
with a set of bona fide stroma-specific transcripts, namely the interstitial 
collagens COL1A1, COL1A2, and COL3A1. Among the top hits were genes involved in 
cellular matrix remodeling and tumor invasion and migration, including 
platelet-derived growth factor receptor beta (PDGFRβ), which was found to be the 
highest-ranking receptor protein genome-wide. Similar analyses performed on ten 
additional TCGA cancer datasets revealed that other tumor types shared CAF 
markers with OSCC, including PDGFRβ, which was found to significantly correlate 
with the reference collagen expression in ten of the 11 cancer types tested. 
Subsequent immunostaining of OSCC specimens demonstrated that PDGFRβ was 
abundantly expressed in stromal fibroblasts of all tested cases (12/12), while 
it was absent in tumor cells, with greater specificity than other known markers 
such as alpha smooth muscle actin or podoplanin (3/11). Overall, this study 
identified PDGFRβ as a novel marker of stromal activation in OSCC, and further 
characterized a list of promising candidate CAF markers that may be relevant to 
other carcinomas. Our novel approach provides for a fast and accurate method to 
identify CAF markers without the need for large-scale immunostaining 
experiments.

DOI: 10.1371/journal.pone.0154645
PMCID: PMC4851360
PMID: 27128408 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared 
that no competing interests exist.


4. J Org Chem. 2006 Nov 24;71(24):9178-82. doi: 10.1021/jo061586w.

Chiral NMR discrimination of piperidines and piperazines using 
(18-crown-6)-2,3,11,12-tetracarboxylic acid.

Lovely AE(1), Wenzel TJ.

Author information:
(1)Department of Chemistry, Bates College, Lewiston, Maine 04240, USA.

Enantiomeric discrimination is observed in the (1)H and (13)C NMR spectra of 
piperidines and piperazines in the presence of 
(-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. The amines are protonated by 
the carboxylic acid groups of the crown ether to produce the corresponding 
ammonium and carboxylate ions. Association of the ammonium ion with the crown 
ether likely involves two hydrogen bonds with the crown ether oxygen atoms and 
an ion pair with the carboxylate anion. Methyl, hydroxymethyl, phenyl, carboxyl, 
pyridyl, and cyclohexyl substituent groups alpha to the nitrogen atom do not 
inhibit binding of the ammonium ion to the crown ether. The NMR spectra of 
piperidines with the stereogenic center alpha or beta to the nitrogen atom 
exhibit substantial enantiomeric discrimination. Dibasic substrates such as the 
piperizines are likely converted to their diprotonated form in the presence of 
the crown ether, and both nitrogen atoms appear to associate with the crown 
ether moiety.

DOI: 10.1021/jo061586w
PMID: 17109544 [Indexed for MEDLINE]


5. Anal Biochem. 1997 Nov 1;253(1):50-6. doi: 10.1006/abio.1997.2349.

Avoiding interferences from Good's buffers: A contiguous series of noncomplexing 
tertiary amine buffers covering the entire range of pH 3-11.

Yu Q(1), Kandegedara A, Xu Y, Rorabacher DB.

Author information:
(1)Department of Chemistry, Wayne State University, Detroit, Michigan 48202, 
USA.

Of the 20 well-known buffers proposed by Good, all but 3 form metal ion 
complexes which can result in serious interferences, particularly in protein 
analyses. The structural features responsible for such complex formation have 
been identified. Based on a mechanistic analysis of the metal complexation 
process, it is proposed that tertiary amine compounds, having N-substituents 
which are ethyl or larger, are sterically inaccessible for initial bond 
formation with solvated metal ions in aqueous solution. Thus, in the absence of 
donor atoms on the alpha-, beta-, or gamma-carbons, metal complexation cannot 
proceed. The proposed noncomplexing compounds include Good's 3 noncomplexing 
buffers (Mes, Mops, Pipes) plus six related species. Mixed-mode acid 
dissociation constants (hydrogen ion in terms of activity, conjugate acid-base 
species in molar concentrations) have been determined for all compounds in their 
protonated form at 25 degrees C, mu = 0.10 M (NaNO3). The values for four 
compounds in this series are reported here for the first time: viz., 
N,N'-diethylpiperazine for which log Ka1m = 4.67 +/- 0. 03 and log Ka2m = 8.83 
+/- 0.02; N,N,N',N'-tetraethylmethylenediamine for which log Ka1m < 1 and log 
Ka2m = 11.01 +/- 0.03; N,N'-diethyl-N,N'-bis(3-sulfopropyl)ethylenediamine for 
which log Ka1m = 5.75 +/- 0.03 and log Ka2m = 9.37 +/- 0.02; and 
piperazine-N,N'-bis(2-ethanesulfonic acid) (Pipes) for which log Ka1m = 2.81 +/- 
0.01 (the value of log Ka2m having been previously reported).

Copyright 1997 Academic Press.

DOI: 10.1006/abio.1997.2349
PMID: 9356141 [Indexed for MEDLINE]