Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Int J Mol Sci. 2024 Oct 9;25(19):10840. doi: 10.3390/ijms251910840.

3,8-Disubstituted Pyrazolo[1,5-a]quinazoline as GABA(A) Receptor Modulators: 
Synthesis, Electrophysiological Assays, and Molecular Modelling Studies.

Crocetti L(1), Guerrini G(1), Melani F(1), Mascia MP(2), Giovannoni MP(1).

Author information:
(1)Neurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, 
Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
(2)CNR-Institute of Neuroscience, Cagliari, Cittadella Universitaria, 09042 
Monserrato, Italy.

As a continuation of our study in the field of GABAA receptor modulators, we 
report the design and synthesis of new pyrazolo[1,5-a]quinazoline (PQ) bearing 
at the 8-position an oxygen or nitrogen function. All the final compounds and 
some intermediates, showing the three different forms of the 
pyrazolo[1,5-a]quinazoline scaffold (5-oxo-4,5-dihydro, -4,5-dihydro, and 
heteroaromatic form), have been screened with an electrophysiological technique 
on recombinant GABAAR (α1β2γ2-GABAAR), expressed in Xenopus laevis oocytes, by 
evaluating the variation in produced chlorine current, and permitting us to 
identify some interesting compounds (6d, 8a, 8b, and 14) on which further 
functional assays were performed. Molecular modelling studies (docking, 
minimization of complex ligand-receptor, and MD model) and a statistical 
analysis by a Hierarchical Cluster Analysis (HCA) have collocated these ligands 
in the class corresponding to their pharmacological profile. The HCA results are 
coherent with the model we recently published (Proximity Frequencies), 
identifying the residues γThr142 and αHis102 as discriminant for the agonist and 
antagonist profile.

DOI: 10.3390/ijms251910840
PMCID: PMC11477267
PMID: 39409169 [Indexed for MEDLINE]

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


2. Org Lett. 2024 Oct 18;26(41):8702-8707. doi: 10.1021/acs.orglett.4c02932. Epub
 2024 Oct 3.

Enantioselective Synthesis of Chiral 1,5-Benzodiazepin-2-ones by Pd-Catalyzed 
Asymmetric Hydrogenation and Reductive Amination.

Guo Q(1), Xie C(1), Zi G(1), Hou G(1).

Author information:
(1)Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal 
University, Beijing 100875, China.

The enantioselective synthesis of chiral 4-substituted 
4,5-dihydro-1H-[1,5]benzodiazepin-2(3H)-ones via asymmetric hydrogenation 
catalyzed by the Pd/f-spiroPhos complex in the presence of hydrochloric acid as 
an additive has been developed, achieving excellent enantioselectivities and 
high turnover numbers, up to 99% ee and TON = 4600. More significantly, the 
asymmetric reductive amination of β-keto esters with 1,2-phenylenediamine has 
also been successfully realized to afford chiral 4-substituted 
4,5-dihydro-1H-[1,5]benzodiazepin-2(3H)-ones with comparable 
enantioselectivities of up to 99% ee.

DOI: 10.1021/acs.orglett.4c02932
PMID: 39360951


3. Molecules. 2024 Aug 30;29(17):4122. doi: 10.3390/molecules29174122.

Two Small Molecule Drugs with Topical Applications, Diflunisal and Naphazoline, 
and Their Potentially Toxic Photodegradants: Analysis by Chemical and Biological 
Methods.

Lejwoda K(1), Gumieniczek A(1), Filip A(2), Naumczuk B(3).

Author information:
(1)Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 
4, 20-090 Lublin, Poland.
(2)Cytogenetics Laboratory, Department of Cancer Genetics, Medical University of 
Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland.
(3)Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 
01-224 Warsaw, Poland.

Because of their topical application in patients and meaningful UV/VIS 
absorptive properties, the degradation and potential toxicity under irradiation 
of diflunisal (DIF) and naphazoline (NAF) were studied. In addition, the impact 
of pH on their photostability was examined, showing the highest degradation of 
acidic DIF at pH 1 and 13 and the highest degradation of basic NAF at pH below 
7. An LC-UV analysis and chemical tests showed the first-order kinetics for 
their degradation and generation of reactive oxygen species (ROS). A 
UPLC-HRMS/MS analysis allowed us to identify four degradants of DIF (from DD-1 
to DD-4) and six degradants of NAF (from ND-1 to ND-6). When Toxtree software 
was used, a high class III of toxicity was observed for DD-2, DD-3, and DD-4, 
and for all the NAF degradants. Furthermore, the ND-2 product, i.e., 
2-[(1-methylnaphthalen-2-yl)methyl]-4,5-dihydro-1H-imidazole, was shown to 
present medium mutagenic and high tumorigenic effects according to OSIRIS 
Property Explorer. In addition, two in vitro tests on BALB/c 3T3 mouse 
fibroblasts showed a phototoxic effect of DIF and NAF at the lowest 
concentrations tested, i.e., 5 µg/mL. Thus, our present results could be useful 
to design further phototoxicity studies for DIF and NAF to minimize the risk of 
phototoxicity due to their photodegradation.

DOI: 10.3390/molecules29174122
PMCID: PMC11396828
PMID: 39274970 [Indexed for MEDLINE]

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


4. Bioorg Med Chem Lett. 2024 Nov 15;113:129952. doi: 10.1016/j.bmcl.2024.129952.
 Epub 2024 Sep 10.

Pyrazolines inhibiting the activity of the early growth response-1 DNA-binding 
domain.

Yoon H(1), Koh D(2), Lim Y(3), Lee YH(4), Lee JK(1), Shin SY(5).

Author information:
(1)Division of Chemical Engineering, Konkuk University, Seoul 05029, Republic of 
Korea.
(2)Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, 
Republic of Korea.
(3)Division of Bioscience and Biotechnology, Konkuk University, Seoul 05029, 
Republic of Korea.
(4)Department of Biological Sciences, Konkuk University, Seoul 05029, Republic 
of Korea.
(5)Department of Biological Sciences, Konkuk University, Seoul 05029, Republic 
of Korea. Electronic address: shinsy@konkuk.ac.kr.

To identify compounds inhibiting the activity of the Early Growth Response 
(EGR)-1 DNA-binding domain, thirty-seven pyrazolines were prepared and their 
EGR-1 DNA-binding activities were measured. Pharmacophores were derived based on 
quantitative structure-activity relationship calculations. As compound 2, 
1-(5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-2-ol, showed the 
best inhibitory effects against the activity of the EGR-1 DNA-binding domain, 
the binding mode between compound 2 and EGR-1 was elucidated using in silico 
docking. The pharmacophores were matched to the binding modes. Electrophoretic 
mobility shift assays confirmed that compound 2 dose-dependently inhibited 
TNFα-induced EGR-1-DNA complex formation in HaCaT cells. Reverse 
transcription-polymerase chain reaction demonstrated that compound 2 effectively 
reduced the mRNA expression of EGR-1-regulated inflammatory genes, including 
thymic stromal lymphopoietin (TSLP), interleukin (IL)-1β, IL-6, and IL-31, in 
TNFα-stimulated HaCaT cells. Therefore, compound 2 could be developed as an 
agent that inhibits the activity of the EGR-1 DNA-binding domain.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.bmcl.2024.129952
PMID: 39265893 [Indexed for MEDLINE]

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.


5. Oxymetazoline.

Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National 
Institute of Child Health and Human Development; 2006–.
2024 Aug 15.

Although no information exists on the use of oxymetazoline specifically during 
breastfeeding, very little should reach the infant through breastmilk because of 
the local administration and limited absorption into the maternal bloodstream. 
It is recommended over oral systemic decongestants such as pseudoephedrine 
during breastfeeding.[1] Topical use on the face for rosacea is unlikely to 
present a risk to the nursing infant.

PMID: 30000423