Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. ACS Omega. 2024 Jul 1;9(28):30751-30770. doi: 10.1021/acsomega.4c03208. 
eCollection 2024 Jul 16.

Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Computational 
Approach of a New Pyrazolo[3,4-g]isoquinoline Derivative as Potent against 
Leucine-Rich Repeat Kinase 2 (LRRK2).

Bakhite EA(1), Mohamed SK(2)(3), Lai CH(4)(5), Subramani K(6), Marae IS(1), 
Abuelhassan S(1), Soliman AAE(1), Youssef MSK(1), Abuelizz HA(7), Mague JT(8), 
Al-Salahi R(7), El Bakri Y(9).

Author information:
(1)Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, 
Egypt.
(2)Chemistry and Environmental Division, Manchester Metropolitan University, 
Manchester M1 5GD, England.
(3)Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, 
Egypt.
(4)Department of Medical Applied Chemistry, Chung Shan Medical University, 
Taichung 40241, Taiwan.
(5)Department of Medical Education, Chung Shan Medical University Hospital, 
Taichung 40201, Taiwan.
(6)Center for Healthcare Advancement, Innovation and Research, Vellore Institute 
of Technology University, Chennai Campus, Chennai 600127, India.
(7)Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
University, Riyadh 11451, Saudi Arabia.
(8)Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, 
United States.
(9)Department of Theoretical and Applied Chemistry, South Ural State University, 
Lenin prospect 76, Chelyabinsk 454080, Russian Federation.

Ethyl-2-((8-cyano-3,5,9a-trimethyl-1-(4-oxo-4,5-dihydrothiazol-2-yl)-4-phenyl-3a,4,9,9a-tetrahydro-1H-pyrazolo[3,4-g]isoquinolin-7-yl)thio)acetate 
(5) was synthesized, and its structure was characterized by IR, MS, and NMR (1H 
and 13C) and verified by a single-crystal X-ray structure determination. 
Compound 5 adopts a "pincer" conformation. In the crystal, the hydrogen bonds of 
-H···O, C-H···O, and O-H···S form thick layers of molecules that are parallel to 
(101). The layers are linked by C-H···π(ring) interactions. The Hirshfeld 
surface analysis shows that intermolecular hydrogen bonding plays a more 
important role than both intramolecular hydrogen bonding and π···π stacking in 
the crystal. The intramolecular noncovalent interactions in 5 were studied by 
QTAIM, NCI, and DFT-NBO calculations. Based on structural activity relationship 
studies, leucine-rich repeat kinase 2 (LRRK2) was found to bind 5 and was 
further subjected to molecular docking studies, molecular dynamics, and ADMET 
analysis to probe potential drug candidacy.

© 2024 The Authors. Published by American Chemical Society.

DOI: 10.1021/acsomega.4c03208
PMCID: PMC11256088
PMID: 39035914

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


2. J Agric Food Chem. 2024 Mar 13;72(10):5403-5415. doi:
10.1021/acs.jafc.3c09142.  Epub 2024 Feb 22.

Decoding Molecular Mechanism Underlying Human Olfactory Receptor OR8D1 
Activation by Sotolone Enantiomers.

Wang J(1)(2)(3), Wang D(1)(2), Huang M(1)(2), Sun B(1)(2)(3), Ren F(3), Wu 
J(1)(2), Zhang J(1)(2), Li H(1)(2), Sun X(1)(2).

Author information:
(1)Key Laboratory of Brewing Molecular Engineering of China Light Industry, 
Beijing Technology & Business University (BTBU), Beijing 100048, China.
(2)Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and 
Business University, Ministry of Education, Beijing 100048, China.
(3)Beijing Advanced Innovation Center for Food Nutrition and Human Health, 
Department of Nutrition and Health, China Agricultural University, Beijing 
100193, China.

Sotolone, a chiral compound, plays an important role in the food industry. 
Herein, (R)-/(S)-sotolone were separated to determine their odor characteristics 
and thresholds in air (R-form: smoky, burned, herb, and green aroma, 0.0514 
μg/m3; S-form: sweet, milk, acid, and nutty aroma, 0.0048 μg/m3). OR8D1 
responses to (R)-/(S)-sotolone were detected in a HEK293 cell-based luminescence 
assay. (S)-Sotolone was a more potent agonist than (R)-sotolone (EC50 values of 
84.98 ± 1.05 and 167.20 ± 0.25 μmol/L, respectively). Molecular dynamics 
simulations and molecular mechanics Poisson-Boltzmann surface area analyses 
confirmed that the combination of (S)-sotolone and OR8D1 was more stable than 
that of (R)-sotolone. Odorant docking, multiple sequence alignments, 
site-directed mutagenesis, and functional studies with recombinant odorant 
receptors (ORs) in a cell-based luminescence assay identified 11 amino-acid 
residues that influence the enantioselectivity of OR8D1 toward sotolone 
significantly and that N2065.46 was indispensable to the activation of OR8D1 by 
(S)-sotolone.

DOI: 10.1021/acs.jafc.3c09142
PMID: 38386648 [Indexed for MEDLINE]


3. J Agric Food Chem. 2022 May 11;70(18):5756-5763. doi:
10.1021/acs.jafc.2c01480.  Epub 2022 Apr 28.

Quantitative Analysis of Lactone Enantiomers in Butter and Margarine through the 
Combination of Solvent Extraction and Enantioselective Gas Chromatography-Mass 
Spectrometry.

Saeki R(1), Yoshinaga K(2), Tago A(1), Tanaka S(1), Yoshinaga-Kiriake A(2)(3), 
Nagai T(4), Yoshida A(4), Gotoh N(1).

Author information:
(1)Department of Food Science and Technology, Tokyo University of Marine Science 
and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan.
(2)Faculty of Food and Agricultural Sciences, Fukushima University, 1 
Kanayagawa, Fukushima 960-1296, Japan.
(3)Department of Life Science, Graduate School of Engineering Science, Akita 
University, 1-1 Tegatagakuen-machi, Akita 010-8502, Japan.
(4)Tsukishima Foods Industry Co. Ltd., 3-17-9 Higashi Kasai, Edogawa-ku, Tokyo 
134-8520, Japan.

Erratum in
    J Agric Food Chem. 2022 Aug 3;70(30):9596. doi: 10.1021/acs.jafc.2c03868.

We quantified the enantiomeric distributions of δ- and γ-lactones in butter, 
fermented butter, and margarine through the combination of solvent extraction 
and enantioselective gas chromatography-mass spectrometry. The main lactones in 
butter and fermented butter comprised (R)-δ-decalactone, (R)-δ-dodecalactone, 
(R)-δ-tetradecalactone, (R)-δ-hexadecalactone, and (R)-γ-dodecalactone. In 
contrast, margarine samples consisted of only δ-decalactone and δ-dodecalactone 
in racemic forms, indicating that synthetic aroma chemicals were added to 
margarine. After heat treatment, 13 types of lactones were detected in butter 
and fermented butter. In heated butter and fermented butter, major δ-lactones in 
the (R)-form were abundant, but only δ-octalactone in the (S)-form was detected. 
In contrast, γ-dodecalactone (main γ-lactone in the heated samples) was abundant 
in the (R)-form, whereas other γ-lactones were detected in the racemic form. 
These results suggested that the major lactones in dairy products are in the 
(R)-form. Furthermore, the heat treatment affected the enantiomeric distribution 
of lactones in butter and fermented butter.

DOI: 10.1021/acs.jafc.2c01480
PMID: 35482605 [Indexed for MEDLINE]


4. ESC Heart Fail. 2021 Aug;8(4):2473-2484. doi: 10.1002/ehf2.13369. Epub 2021
Jun  10.

Readmission following both cardiac and non-cardiac acute dyspnoea is associated 
with a striking risk of death.

Čerlinskaitė K(1)(2)(3), Mebazaa A(2)(3)(4), Cinotti R(5), Matthay M(6)(7), 
Wussler DN(8), Gayat E(2)(3)(4), Juknevičius V(1)(9), Kozhuharov N(8), Dinort 
J(8), Michou E(8), Gualandro DM(8), Palevičiūtė E(1)(9), Alitoit-Marrote I(9), 
Kablučko D(9), Bagdonaitė L(10)(11), Balčiūnas M(1)(9), Vaičiulienė D(12), 
Jonauskienė I(12), Motiejūnaitė J(12), Stašaitis K(12), Kukulskis A(12), 
Damalakas Š(12), Laucevičius A(1), Mueller C(8), Kavoliūnienė A(12), Čelutkienė 
J(1)(9); GREAT network.

Author information:
(1)Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, 
Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
(2)Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), 
Paris, France.
(3)Department of Anesthesiology and Critical Care, Hôpitaux Universitaires Saint 
Louis-Lariboisière, Assistance Publique des Hopitaux de Paris, 2 Rue Ambroise 
Paré, Paris, 75010, France.
(4)Université de Paris, Paris, France.
(5)Department of Anesthesia and Critical Care, Hôpital Laennec, University 
Hospital of Nantes, Saint-Herblain, France.
(6)Department of Medicine and Anesthesia, University of California, San 
Francisco, CA, USA.
(7)Cardiovascular Research Institute, University of California, San Francisco, 
CA, USA.
(8)Cardiology Department and Cardiovascular Research Institute Basel (CRIB), 
University Hospital Basel, University of Basel, Basel, Switzerland.
(9)Centre of Cardiology and Angiology, Vilnius University Hospital Santaros 
Klinikos, Vilnius, Lithuania.
(10)Institute of Biomedical Science, Faculty of Medicine, Vilnius University, 
Vilnius, Lithuania.
(11)Centre of Laboratory Medicine, Vilnius University Hospital Santaros 
Klinikos, Vilnius, Lithuania.
(12)Lithuanian University of Health Sciences, Kaunas, Lithuania.

AIMS: Readmission and mortality are the most common and often combined endpoints 
in acute heart failure (AHF) trials, but an association between these two 
outcomes is poorly investigated. The aim of this study was to determine whether 
unplanned readmission is associated with a greater subsequent risk of death in 
patients with acute dyspnoea due to cardiac and non-cardiac causes.
METHODS AND RESULTS: Derivation cohort (1371 patients from the LEDA study) and 
validation cohort (1986 patients from the BASEL V study) included acute dyspnoea 
patients admitted to the emergency department. Cox regression analysis was used 
to determine the association of 6 month readmission and the risk of 1 year 
all-cause mortality in AHF and non-AHF patients and those readmitted due to 
cardiovascular and non-cardiovascular causes. In the derivation cohort, 666 
(49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. 
Six month readmission was associated with an increased 1 year mortality risk in 
both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence 
interval, CI 2.2-4.0), P < 0.001] and the validation cohort (aHR 1.8, 95% CI 
1.4-2.2, P < 0.001). The significant association was similarly observed in AHF 
(aHR 3.2, 95% CI 2.1-4.9, P < 0.001) and other causes of acute dyspnoea (aHR 
2.9, 95% CI 1.9-4.5, P < 0.001), and it did not depend on the aetiology [aHR 
2.2, 95% CI 1.6-3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9-5.7 for 
non-cardiovascular readmissions (P < 0.001 for both)] or timing of readmission. 
CONCLUSION​S: Our study demonstrated a long-lasting detrimental association 
between readmission and death in AHF and non-AHF patients with acute dyspnoea. 
These patients should be considered 'vulnerable patients' that require 
personalized follow-up for an extended period.

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
behalf of European Society of Cardiology.

DOI: 10.1002/ehf2.13369
PMCID: PMC8318470
PMID: 34110099 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed the ICMJE uniform 
disclosure form at www.icmje.org/coi_disclosure.pdf. K.Č., A.M., V.J., E.P., 
I.M., D.K., L.B., M.B., D.V., I.J., J.M., K.S., Audrys K., Š.D., A.L., Aušra K., 
and J.Č. declare that they received financial support from Research Council of 
Lithuania for the submitted work. A.M. received speaker's honoraria from Orion, 
Otsuka, Philips, Roche, and Servier. A.M. received fee as a member of advisory 
board and/or steering committee and/or research grant from Adrenomed, Epygon, 
Neurotronik, Roche, Sanofi, and Sphyngotec. A.M. owns shares in S‐Form Pharma. 
M.M. reports grants from NIH/NHLBI, Department of Defence, NIH/FDA, Bayer 
Pharmaceuticals, and GlaxoSmithKline and personal fees from CS Berhling, 
Boerhinger Ingelheim, Cerus Therapeutics, Roche Genentec, Quark Pharmaceuticals, 
and Thesan Pharamceuticals, outside the submitted work. E.G. received research 
grants from Sphingotec, Deltex Medical, and Retia Medical and consultancy fees 
from Magnisense, Roche Diagnostics, and Adrenomed. C.M. has received research 
support from the Swiss National Science Foundation, the Swiss Heart Foundation, 
the Kommission für Technologie und Innovation, the Stiftung für kardiovaskuläre 
Forschung Basel, Abbott, Alere, Amgen, AstraZeneca, Beckman Coulter, Biomerieux, 
Brahms, Roche, Siemens, Singulex, Sphingotec, the University of Basel, and the 
University Hospital Basel, as well as speaker honoraria/consulting honoraria 
from Abbott, Alere, AstraZeneca, Biomerieux, Boehringer Ingelheim, BMS, Brahms, 
Cardiorentis, Novartis, Roche, Siemens, Sanofi, and Singulex. Aušra K. received 
speaker honoraria from Servier, Bayer, Berlin‐Chemie Menarini, Pfizer, and KRKA. 
Audrys K. received fee as member of Steering Committee Cardiorentis, Novartis, 
and Servier. J.Č. received investigator and speaker fees from Sanofi, Amgen, 
Novartis, Roche Diagnostics, Servier, and AstraZeneca. Other authors declared no 
conflicts of interest.


5. Chemistry. 2017 Mar 13;23(15):3595-3604. doi: 10.1002/chem.201604891. Epub
2016  Dec 29.

Effects of Chlorination on the Tautomeric Equilibrium of 2-Hydroxypyridine: 
Experiment and Theory.

Calabrese C(1), Maris A(1), Uriarte I(2), Cocinero EJ(2), Melandri S(1).

Author information:
(1)Dipartimento di Chimica "G. Ciamician", Università degli Studi di Bologna, 
Via Selmi 2, 40126, Bologna, Italy.
(2)Dpto. Química Física, Universidad del País Vasco (UPV/EHU), Apartado 644, 
48080, Bilbao, Spain.

The effects of halogenation on the tautomeric and conformational equilibria of 
the model system 2-hydroxypyridine/2-pyridone have been investigated through 
chlorine substitution at positions 3, 4, 5, and 6. In the gas phase, the lactim 
syn-periplanar tautomer (OHs ) was the predominant species for all compounds 
over the lactam form (C=O) and the less abundant anti-periplanar lactim (OHa ). 
However, the population of the three species was shown to be dependent on the 
position of the chlorine substitution. Chlorination in position 5 or 6 strongly 
stabilizes the OHs tautomer, whereas the C=O form has a significant population 
when the ring is chlorinated in positions 3 or 4. Overall, the OHa form is the 
least favourable form, although the 3-substitution favours the population of 
this tautomer. In addition, the C=O tautomer is strongly stabilized in the 
solvent, which makes it the dominant form in some substituted species. This 
study has been performed by means of rotational spectroscopy in the gas phase 
and/or theoretical calculations in the isolated phase and in solution. Both the 
OHs and C=O forms of 5-chloro-2-hydroxypyridine and the OHs form of 
6-chloro-2-hydroxypyridine were experimentally observed. All transitions 
displayed a complex nuclear hyperfine structure owing to the presence of the 
chlorine and nitrogen nuclei. For all species, a full quadrupolar hyperfine 
analysis has been performed. This has provided crucial information for the 
unambiguous identification of tautomers.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI: 10.1002/chem.201604891
PMID: 28032669