Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Inorg Chem. 2024 Nov 7. doi: 10.1021/acs.inorgchem.4c04050. Online ahead of 
print.

Tuning the Properties of Rigidified Acyclic DEDPA(2-) Derivatives for 
Application in PET Using Copper-64.

Torralba-Maldonado D(1), Marlin A(2), Lucio-Martínez F(3), Freire-García A(3), 
Whetter J(2), Brandariz I(3), Iglesias E(3), Pérez-Lourido P(4), Ortuño RM(1), 
Boros E(2), Illa O(1), Esteban-Gómez D(3), Platas-Iglesias C(3).

Author information:
(1)Departament de Química, Universitat Autònoma de Barcelona, 08193, Cerdanyola 
del Vallès, Spain.
(2)Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 
53706, United States.
(3)Centro Interdisciplinar de Química e Bioloxía (CICA) and Departamento de 
Química, Facultade de Ciencias, Universidade da Coruña, Galicia, 15071 A Coruña, 
Spain.
(4)Departamento de Química Inorgánica, Facultad de Química, Universidade de 
Vigo, As Lagoas, Marcosende, 36310 Pontevedra, Spain.

We present a detailed investigation of the coordination chemistry toward 
[natCu/64Cu]copper of a series of H2DEDPA derivatives (H2DEDPA = 
6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing 
cyclohexyl (H2CHXDEDPA), cyclopentyl (H2CpDEDPA) or cyclobutyl (H2CBuDEDPA) 
spacers. Furthermore, we also developed a strategy that allowed the synthesis of 
a H2CBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl 
ring, which can be used for conjugation to targeting units. The X-ray structures 
of the Cu(II) complexes evidence distorted octahedral coordination around the 
metal ion in all cases. Cyclic voltammetry experiments (0.15 M NaCl) evidence 
quasi-reversible reduction waves associated with the reduction of Cu(II) to 
Cu(I). The complexes show a high thermodynamic stability, with log KCuL values 
of 25.11(1), 22.18(1) and 20.19(1) for the complexes of CHXDEDPA2-, CpDEDPA2- 
and CBuDEDPA2-, respectively (25 °C, 1 M NaCl). Dissociation kinetics 
experiments reveal that both the spontaneous- and proton-assisted pathways 
operate at physiological pH. Quantitative labeling with 64CuCl2 was observed at 
0.1 nmol for CHXDEDPA2- and CpDEDPA2-, 0.025 nmol for CBuDEDPA2- and 1 nmol for 
CBuDEDPA-NHBoc2-, with no significant differences observed at 15, 30, and 60 
min. The radio-complexes are stable in PBS over a period of 24 h.

DOI: 10.1021/acs.inorgchem.4c04050
PMID: 39508185


2. Nanoscale. 2024 Nov 7. doi: 10.1039/d4nr03140g. Online ahead of print.

Minimizing defect states through multidentate coordination and morphology 
regulation for enhancing the performance of inverted perovskite solar cells.

Baishya H(1), Patel MJ(2), Das Adhikari R(1), Yadav D(2), Iyer PK(1)(2).

Author information:
(1)Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 
781039, Assam, India. pki@iitg.ac.in.
(2)Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 
781039, Assam, India.

The diversity of the defects present in perovskite materials negatively impacts 
both the power conversion efficiency (PCE) and the long-term stability of 
perovskite solar cells (PSCs). The chemical passivation of these defects has 
been addressed through a multifunctional molecule, 
4-((trifluoromethyl)thio)benzoic acid, that contains the carbonyl (CO) group, 
which exhibits a strong passivation effect by interacting with both the organic 
cation (FA+) and uncoordinated Pb2+ ionic defects while the sulfur (S) 
heteroatom passivates Pb2+ defects at the grain boundary and on the surfaces of 
the perovskite layer. Additionally, the CF3 group protects the perovskite film 
from ambient degradation as well as stabilizing the perovskite framework by 
forming hydrogen and coordination bonds with the FA+ cation and Pb2+ ions, 
respectively. The interaction between CO and Pb2+ forms a Lewis acid-base 
adduct that regulates grain growth during crystallization, enhancing the 
perovskite film's surface morphology as confirmed by SEM, AFM, and PL mapping. 
This reduces trap-assisted recombination of charged carriers, thereby enhancing 
their lifetime and transport, as observed from TRPL, KPFM, and c-AFM analyses. 
As a result of the combined effect of the additive molecule, the optimized 
device showed a marked improvement in efficiency rising from 16.54% in the 
pristine device to 20.87% with a reduction in hysteresis. Moreover, the 
optimized device shows enhancement of stability by retaining ∼86% normalized PCE 
after 40 days of storage under ambient conditions at 25 ± 3 °C and a relative 
humidity of ∼45-55%.

DOI: 10.1039/d4nr03140g
PMID: 39508081


3. Front Pharmacol. 2024 Oct 23;15:1448744. doi: 10.3389/fphar.2024.1448744. 
eCollection 2024.

Identification of human pregnane X receptor antagonists utilizing a 
high-throughput screening platform.

Lynch C(1), Margolis R(1), Niebler J(1), Travers J(1), Sakamuru S(1), Zhao T(1), 
Klumpp-Thomas C(1), Huang R(1), Xia M(1).

Author information:
(1)National Center for Advancing Translational Sciences, National Institutes of 
Health, Bethesda, MD, United States.

Pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor with a 
well-established role in regulating drug metabolism and clearance. Recent 
studies have shown that PXR is involved in cell proliferation, apoptosis, immune 
response, and energy homeostasis. It is important to identify compounds that may 
modulate PXR activity to prevent drug-drug interactions, distinguish chemicals 
which could potentially generate toxicity, and identify compounds for further 
development towards therapeutic usage. In this study, we have screened the 
National Center for Advancing Translational Sciences (NCATS) Pharmacologically 
Active Chemical Toolbox (NPACT) library, which consists of 5,099 unique 
pharmacologically active synthetic and naturally derived small molecules to 
identify PXR antagonists. Ninety-four compounds were identified as potential PXR 
antagonists through a primary screen and 66 were confirmed in a confirmation 
study. Of these compounds, twenty potential PXR antagonists, including 
gamma-secretase modulator 2 (GSM2) and fusidic acid, were selected for further 
study based on their efficacy, potency, and novelty. Their PXR inhibition 
abilities were assessed by examining their effects on cytrochrome P450 (CYP) 3A4 
mRNA expression using metabolically competent HepaRG cells. Additionally, a 
pharmacological inhibition assay using various concentrations of rifampicin as a 
stimulator was performed in HepG2-CYP3A4-hPXR cells to confirm the activity of 
the 20 selected compounds against PXR. Finally, HepaRG cells were used to 
confirm PXR antagonism by verification of a concentration-dependent decrease of 
CYP3A4 when co-treated with the known PXR agonist, rifampicin. Additionally, the 
potent actives were further investigated using molecular docking to find the 
potential interactions of the novel ligands with the active sites of hPXR. To 
our knowledge from the current study, GSM2 and fusidic acid have been identified 
as novel PXR antagonists, which provides useful information for further 
investigation regarding possible drug-drug interactions, as well as the 
detection of potential therapeutic effects or other toxic consequences.

Copyright © 2024 Lynch, Margolis, Niebler, Travers, Sakamuru, Zhao, 
Klumpp-Thomas, Huang and Xia.

DOI: 10.3389/fphar.2024.1448744
PMCID: PMC11537999
PMID: 39508053

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest. The author(s) declared that 
they were an editorial board member of Frontiers, at the time of submission. 
This had no impact on the peer review process and the final decision.


4. Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Sep 20;55(5):1195-1201. doi: 
10.12182/20240960403.

[Effects of Ionizing Radiation on Intestinal Bile Acid Metabolism: Mechanism of 
the Radioprotective Effect of Glycoursodeoxycholic Acid].

[Article in Chinese]

Dai J(1), Gao Y(1), Wang J(1), Zhang S(1), Liu P(1).

Author information:
(1)（ 214400） Jiangyin Clinical College, Xuzhou Medical University, Wuxi 214400, 
China.

OBJECTIVE: Radioactive intestinal injury is a common complication during 
radiotherapy of tumors. The aim of this study is to observe the effect of 
ionizing radiation on short-term changes in intestinal bile acids and to 
investigate the radioprotective effect of bile acids on intestinal cells.
METHODS: A rat model of small intestinal injury was constructed by exposing the 
abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile 
acids were quantified using metabolomics analysis. IEC-6 cells, a small 
intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) 
control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid 
(GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO 
irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation 
group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was 
assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow 
cytometry. The colony formation rate and the radiosensitivity of the cells were 
determined by colony formation assay on solid media. The expression levels of 
proteins associated with cell death were determined using Western blot.
RESULTS: After exposure to irradiation, the small intestine tissues of the rats 
showed typical radioactive intestinal injury. In addition, various bile acids 
showed fluctuation before and after irradiation. Among the bile acids, GUDCA 
increased significantly at 3 d after irradiation, but returned to the 
pre-irradiation level at 7 d after irradiation. Compared with the control group, 
after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after 
irradiation was significantly higher than that of the DMSO group (P<0.05); the 
expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, 
were significantly lower than those in the control group (P<0.05). After GUDCA 
treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells 
after irradiation was lower than that of the DMSO group (P<0.05). Compared with 
the DMSO control group, the colony formation ability of the GUDCA experimental 
group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 
6 Gy (P<0.05). D0, or the mean lethal dose, of the GUDCA group was 6.374, while 
that of the DMSO group was 4.572. Compared with the DMSO control group, the D0 
value of the GUDCA treatment group increased, and the sensitization enhancement 
ratio (SER) was 0.717.
CONCLUSION: After exposing the abdomen of rats to irradiation, the intestinal 
bile acid metabolism of the rats will change significantly, and GUDCA can 
produce radioprotective effects on intestinal cells to a certain extent.

© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of 
Sichuan University (Medical Sciences).

DOI: 10.12182/20240960403
PMCID: PMC11536250
PMID: 39507959 [Indexed for MEDLINE]

Conflict of interest statement: 
利益冲突　本文作者张舒羽是本刊编委会编委。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。


5. Front Nutr. 2024 Oct 23;11:1440896. doi: 10.3389/fnut.2024.1440896.
eCollection  2024.

Association between dried fruit intake and kidney function: research from 
univariate and multivariate Mendelian randomized studies.

Gao Y(#)(1), Yue X(#)(2), Zhao W(#)(3), Yuan F(3).

Author information:
(1)The First Clinical College, Liaoning University of Traditional Chinese 
Medicine, Shenyang, China.
(2)The Second Clinical College, Liaoning University of Traditional Chinese 
Medicine, Shenyang, China.
(3)Department of Nephropathy, The First Affiliated Hospital of Liaoning 
University of Traditional Chinese Medicine, Shenyang, China.
(#)Contributed equally

OBJECTIVES: Observational studies have identified an association between dried 
fruit intake and kidney function. However, these studies have limitations such 
as vulnerability to confounders and reverse causality bias. Therefore, this 
study aimed to explore the potential causal relationship between dried fruit 
intake and kidney function.
METHODS: A two-sample Mendelian randomization (MR) study was conducted using a 
large-scale genome-wide association study dataset to investigate the causal 
relationship between dried fruit intake and kidney function markers (blood urea 
nitrogen (BUN), creatinine (CR), uric acid (UA), cystatin C (CyC), hematuria, 
microalbuminuria). The main analytical method was inverse variance weighting. In 
addition, we applied the MR Egger and weighted median to assess the robustness 
of the results. Finally, Multivariate Mendelian randomization (MVMR) was used to 
estimate the direct effect of dried fruit intake on kidney function markers.
RESULTS: The univariate MR analysis showed that increased dried fruit intake was 
associated with lower kidney function markers, including BUN (β: -0.171, 95% 
confidence interval (CI): -0.239 to -0.102, p = 1.063 × 10-6), CR (β: -0.205, 
95% CI: -0.311 to -0.099, p = 1.455 × 10-4), UA (β = -0.317, 95% CI: -0.384 to 
-0.249, p = 4.439 × 10-20), and CysC (β = -0.323, 95% CI: -0.384 to -0.249, 
p = 1.074 × 10-11); however, it was unrelated to hematuria and microalbuminuria. 
Causality persisted after performing MVMR analysis; however, with the addition 
of alcohol consumption and smoking as exposure factors, the causality for UA 
(β = -0.296, 95% CI: -0.523 to -0.068, p = 1.094 × 10-2) and CysC (β = -0.238, 
95% CI: -0.465 to -0.011, p = 4.024× 10-2) weakened, while the causality for BUN 
(β = -0.038, 95% CI: -0.215 to 0.138, p = 6.698 × 10-1) and CR (β = -0.038, 95% 
CI: -0.431 to 0.046, p = 1.347 × 10-1) disappeared.
CONCLUSION: Increased dried fruit intake was associated with lower kidney 
function markers (BUN, CR, UA, and CysC) in the absence of smoking and alcohol 
consumption; however, the causal relationship between dried fruit intake and BUN 
and CR disappeared in the presence of smoking and alcohol consumption. These 
results provide a promising avenue for delaying the course of chronic kidney 
disease.

Copyright © 2024 Gao, Yue, Zhao and Yuan.

DOI: 10.3389/fnut.2024.1440896
PMCID: PMC11537924
PMID: 39507905

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest.