PEST MANAGEMENT SCIENCE
·
2018
·Vol. 75
·期 4
·1045-1055
·
IF 3.249
An-jia Wang,Kai-Xin Zhang,Yu-lin Gao,Ai-zhen Weng,Liu-yang Wang,Yun-hui Zhang,Zhi Zhang,Dong-mei She,Jun Ning,Xiang-dong Mei
BACKGROUND Diamondback moth, Plutella xylostella L., is a very important pest of cruciferous vegetables causing excessive economic losses worldwide. Bioactivities of halo-, diazo-, and cyclopropane acetates of P. xylostella sex pheromone have been evaluated using electrophysiology and enzyme inhibition assays. RESULTS A total of 23 sex pheromone analogs of P. xylostella were designed and synthesized and the result shows that (11 Z )-hexadec-11-en-1-yl 2,2,2-trifluoroacetate, (11 Z )-hexadec-11-en-1-yl 2,2,3,3,3-pentafluoropropanoate, and (11 Z )-hexadec-11-en-1-yl trifluoromethanesulfonate elicited potential inhibitory effects at all doses tested in the electrophysiology and enzyme inhibition assays. Interference of locating the sex pheromone source was found strongest when these three analogs were mixed with the sex pheromone at a 10:1 ratio. In addition, field test showed that the rate of mating disruption was over 90% when (11 Z )-hexadec-11-en-1-yl 2,2,2-trifluoroacetate or (11 Z )-hexadec-11-en-1-yl 2,2,3,3,3-pentafluoropropanoate was mixed with the sex pheromone at a 10:1 ratio. CONCLUSION Two sex pheromone antagonists were screen out by electrophysiology, enzyme inhibition assays, wind tunnel and field tests. We believe that these antagonists could be used to establish a novel eco-friendly measure to control P. xylostella and provide evidence for clarifying the specific functions and molecular mechanisms of sex pheromone antagonists. © 2018 Society of Chemical Industry
研究领域:
昆虫学
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农业科学
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有机化学
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DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
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2019
·Vol. 19
·期 8
·992-1001
·
IF 2.18
Yu Ming-Jun,Yao Sen,Li Ting-Ting,Yang Rui,Yao Ri-Sheng
Background: Cancer patients treated with targeted anti-cancer drug suffer from itch or pruritus. Itch or pruritus is an unpleasant sensation that brings about a negative impact on quality of life, and serious itch may lead to dose reduction and even discontinuation. Gastrin releasing
peptide receptor (GRPR) plays a critical role in itch, inflammation and cancer, and GRPR antagonist has obvious effect on cancer, inflammation and itch. The aim of this paper is to develop a new agent with anti-cancer and anti-itch activity. Methods: A series of GRPR antagonist PD176252
analogues (3a-3l) were designed and synthesized. Both anticancer and anti-itch activities were evaluated. Anti-cancer activity was evaluated in three human cancer cell lines in vitro, the anti-itch activity in evaluated with Kunming mice by intrathecal injection of chloroquine phosphate as
a modeling medium. And the cytotoxicity on normal cells was evaluated. Results: Of the tested compounds, compound 3i showed potently anti-cancer activity to all cancer cell lines tested with IC50 values of 10.5μM (lung), 11.6μM (breast) and 12.8μM (liver) respectively and it
also showed significant inhibition of the scratching behavior. Comparing with PD17625, compound 3i and 3g gave better inhibition activities against all cancer cell lines, compound 3b, 3c and 3i showed better anti-itch activity. The compound 3i is safe for normal breast and liver normal cells,
but it has high cytotoxicity on normal lung cell. Conclusion: The synthesized compounds have dual anti-cancer and anti-itch activity, so the development of drug with dual anti-tumor and anti-itch property is possible.
研究领域:
肿瘤学
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药理学
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医学
✓ 已验证
DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Danqi Sheng,Chen-Xi Yue,Fei Jin,Yao Wang,Muneyoshi Ichikawa,Ye Yu,Chang-Run Guo,Motoyuki Hattori
P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. We determined the cryogenic electron microscopy (cryo-EM) structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5'-phosphate derivatives, pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) and pyridoxal phosphate-6-azophenyl-2′,5′-disulfonic acid (PPADS), and performed structure-based mutational analysis by patch-clamp recording as well as molecular dynamics (MD) simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo- and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes.
研究领域:
分子生物学
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药物研发
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神经科学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
·
IF 9.221
Zhirun Ji,Zhaoyang Shang,Muhammad Sohail,Pei Wang,Bingzhi Li,Xing Zhang,Guoxiang Chen
Protamine, an arginine-rich polycationic peptide, is a natural food preservative and the only approved antidote to heparin overdose. The detection of protamine is meaningful; however, the detection of protamine is difficult due to the lack of aromatic amino acids in its composition . Herein, we proposed a fluorometric biosensor for the sensitive detection of protamine based on the protamine-mediated regulation of CRISPR/Cas12a collateral cleavage. In the absence of protamine, the DNA probe specifically hybridizes with the Cas12a-crRNA complex, causing the activation of Cas12a. In the presence of protamine, positively charged protamine tightly binds to negatively charged DNA probes through electrostatic interaction , so that the DNA probe cannot hybridize with the Cas12a-crRNA complex. Using a short ssDNA modified with fluorophore and quencher as a reporter, the information of protamine concentration is transduced into DNA information and sensed in a signal turn-off manner. The linear range of this method in protamine detection is 0.04–3.2 μg/mL, yielding a detection limit of 0.03 μg/mL, and the entire sampling-to-response time is about 1 h. This biosensor provides a rationale for using the programmable nuclease Cas12a to detect protamine, and further advances the application of CRISPR technology in bioanalyses.
研究领域:
生物化学
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分子生物学
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医学检测
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产品关联
DOI
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 8
·628-635
·
IF 1.164
Siyun Nian,Xia Gan,Xiangduan Tan,Zhenpeng Yu,Panfeng Wang,Xing Chen,Guoping Wang
Fourteen novel compounds were prepared and their antagonistic activities against liver X receptors (LXR) α/β were tested in vitro. Compound 26 had an IC50 value of 6.4 µM against LXRα and an IC50 value of 5.6 µM against LXRβ. Docking studies and the results of structure–activity relationships support the further development of this chemical series as LXRα/β antagonists.
研究领域:
药理学
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分子生物学
✓ 已验证
DOI
高影响因子
Applied Food Research
·
2025
·
IF 6.2
Guodong Shan,Xiuqin Fan,Qingcheng Wang,Li Zhang,Lijun Ge,Weibo Lu,Jing Xue,Kang Chen,Zejun Wang,Qing Shen
The inappropriate use of H2 receptor antagonists (H2RAs) in functional foods (FFs) and food-medicine homology materials (FMHs) designed to enhance gastrointestinal function (IGF) presents health risks due to potential adverse effects. In this study, an analytical method that integrates Captiva EMR-Lipid (CEL) solid-phase extraction (SPE) with liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for the detection of H2RAs (nizatidine, famotidine, cimetidine, ranitidine, and lafutidine) in these products. Through the optimization of CEL-SPE parameters, such as using 200 mg of sorbent and eluting with ACN/water (80/20, v/v), the recovery rates of H2RAs in IGF-FF and IGF-FMH ranged from 87.4 % to 94.6 % and 90.2 % to 97.1 %, respectively. The assessment of matrix effects revealed that the five H2RAs exhibit matrix suppression, necessitating the construction of matrix-matched standard curves with correlation coefficients (r 2 ) exceeding 0.9991. The detection limits ranged from 0.4 to 0.8 μg·kg −1 and the quantification limits ranged from 1.3 to 2.7 μg·kg −1 , with recovery rates spanning from 85.4 % to 97.1 % and relative standard deviations ≤ 15 %. The successful development of this technique not only helps safeguard consumer health but also provides scientific basis and technical support for market supervision, thereby preventing and addressing food safety risks.
研究领域:
食品安全
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分析化学
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药物检测
✓ 已验证
产品关联
DOI
高影响因子
NEUROPHARMACOLOGY
·
2018
·
IF 4.249
Ruirui Qi,Yang Su,Leilei Pan,Yuqi Mao,Lu Liang,Zhiqiang Dai,Junqin Wang,Yiling Cai
Enhanced cholinergic activity contributes to the production of complex autonomic manifestations of motion sickness (MS). However, whether anti-cholinergics exert their anti-MS effects through central or peripheral actions remained unclarified. In the present study, we investigated the effects of mecamylamine (MEC) and scopolamine (SCOP) on rotation-induced gastrointestinal symptoms (conditioned gaping and defecation), locomotion disturbances (hypoactivity and impaired balance performance), hypothermia as well as Fos expression in vestibulo-autonomic regions in rats. We also observed the effects of hexamethonium (HEX) and methyl scopolamine (MSCP) on those MS behavioral responses. The efficacy of all these drugs on rotation-induced emesis and other MS symptoms in cats was also examined. We found that intragastric administration of MEC and SCOP inhibited rotation-induced gaping and defecation in rats, but only MEC showed a dose-dependent manner. MEC aggravated rotation-induced balance disorder and failed to attenuate rotation-induced hypothermia as the SCOP did. MEC was more effective for inhibiting Fos expression in the caudal vestibular nucleus and nucleus of solitary tract than SCOP. Intraperitoneal injection of HEX and MSCP also significantly alleviated rotation-induced gastrointestinal symptoms, and showed benefit to balance performance in rats. In cats, MEC, SCOP and HEX had prophylactic effects against rotation-induced emesis and salivation, and deceased non-retching/vomiting symptoms, but MSCP only attenuated emesis. It suggested that MEC and SCOP might alleviate gastrointestinal symptoms of MS via inhibiting peripheral autonomic nervous system and central vestibulo-autonomic pathways. The nicotinic acetylcholine receptor inhibitors like MEC might be new candidates against gastrointestinal symptoms induced by MS or other vestibular disorders .
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Liju Yu,Jie Gao,Tingting Deng,Chang Gao,Jiaxing Wang,Nan Wang
Heart failure is a global epidemic characterized by high mortality and morbidity rates. β1-Adrenoceptors (ADRβ1) antagonists are the main drugs used in the treatment of HF. A simple and convenient method for screening ADRβ1 antagonists is necessary. Nebivolol has four chiral centers, and its byproducts, which are not easy to avoid, may interact with ADRβ1. Cell membrane chromatography based on SNAP-tag technology provides a comprehensive solution. In this study, an ADRβ1 target cell membrane chromatography model based on SNAP-tag technology was established, and the selectivity, specificity, repeatability, and column life of the system were validated. Under optimized conditions, this model was used to screen for active components targeting ADRβ1 in nebivolol and its byproducts. The bioactivity of nebivolol and its byproducts was detected by calcium influx. The results showed that the ADRβ1 SNAP-tag/CMC model was successfully established and could be used to screen active drugs targeting ADRβ1. Among nebivolol and its byproducts, D-nebivolol (SRRR-enantiomer) had the best affinity for ADRβ1. Three byproducts of nebivolol also exhibited retention characteristics on ADRβ1. In vitro calcium influx experiments verified the interaction of these components with ADRβ1, showing good inhibitory effects on ADRβ1. In conclusion, the ADRβ1 SNAP-tag/CMC model developed in this study can be used for the comprehensive screening of active components targeting ADRβ1 in complex samples.
研究领域:
药理学
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药物筛选
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 11
·2400
·
IF 4.6
Ming Yuan,Huai Wang,Mingjun Yu,Sen Yao,Risheng Yao
Cisplatin (CIS) is a widely used chemotherapeutic agent that is highly effective against various cancers. However, its clinical application is frequently limited by its substantial nephrotoxic side effects. The gastrin-releasing peptide receptor (GRPR), a critical regulator in inflammatory diseases, has been identified as a promising therapeutic target. Our previous studies have demonstrated that the GRPR antagonists PD176252 and RH-1402 can mitigate CIS-induced nephrotoxicity through anti-inflammatory mechanisms. Based on these findings, we designed and synthesized a series of 2-arylpropanoic acid-L-tryptophan derivatives to enhance the therapeutic effects. Among these compounds,3mexhibited superior renal protection by significantly improving mouse renal tubular epithelial cell (mRTEC) viability from 50.2 ± 2.6% to 80.5 ± 3.9%, surpassing PD176252 (70.8 ± 1.4%) and RH-1402 (73.9 ± 3.7%). Moreover, compound3mmarkedly reduced the expression of kidney injury molecule-1 (KIM-1) and inflammatory cytokines [Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1)]. Finally, molecular docking results revealed that3mexhibited a high binding affinity for GRPR. Computational predictions using SwissADME further indicated that3mpossesses favorable drug-like properties, thereby supporting its potential as a promising candidate for mitigating CIS-induced nephrotoxicity.
研究领域:
药理学
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肿瘤学
·
毒理学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2019
·
IF 6.054
Deyu Kong,Tao Xue,Bin Guo,Jianjun Cheng,Shunyin Liu,Jianhai Wei,Zhengyu Lu,Haoran Liu,Guoqing Gong,Tian Lan,Wenhao Hu,Yushe Yang
P2Y12 antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y12 antagonist AZD1283, a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-methyl group led to lactone analogues of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure–pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-methyl substituent to the piperidinyl moiety. Compound 58l displayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, 58l showed a safety profile that was superior to what was observed for clopidogrel in a rat tail-bleeding model. These results support the further evaluation of compound 58l as a promising drug candidate.
研究领域:
药理学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2022
·Vol. 12
·期 1
·1-13
·
IF 9.584
Liu Qiang,Lei Xiaohua,Cao Zhenyu,Zhang Ju,Yan Likun,Fu Jie,Tong Qing,Qin Wei,Shao Yaoli,Liu Chun,Liu Zhiqiang,Wang Zicheng,Chu Yuan,Xu Ge,Liu Siyuan,Wen Xueyi,Yamamoto Hirofumi,Mori Masaki,Liang Xin. M.,Xu Xundi
Background Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. Methods The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8 −/− (KO) fibrotic mice after carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments. Results Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl 4 - and BDL- treated TRPM8 −/− mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo. Conclusions These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis. Graphical Abstract
研究领域:
肝病学
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分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Han Zhou,Tao Hou,Zhenhua Gao,Xiujie Guo,Chaoran Wang,Jixia Wang,Yanfang Liu,Xinmiao Liang
Ethnopharmacological relevance Dopamine receptors are long-standing primary targets in the treatment of mental diseases and there is growing evidence that suggests relationships between obesity and the dopamine system, especially dopamine D1 and D2 receptors. Leaves of Nelumbo nucifera Gaertn. (lotus leaves) have been medically used for helping long-term maintenance of weight loss. Whether and how components of lotus leaves function through the dopamine receptors remains unclear. Aim of the study This work aimed to discover dopamine receptor-active alkaloids isolated from the lotus leaves, to evaluate their potencies and to analyze their structure activity relationship . Materials and methods Dried lotus leaves were prepared and total extract was divided into alkaloids and flavones . Eight alkaloids were separated and characterized by a combination of high-performance liquid chromatography, quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance, and assayed by a fluorometric imaging plate reader platform. Human embryonic kidney 239 cell lines expressing dopamine D1, D2 and serotonin 2A (5-HT2A) receptors, respectively, were cultured and used in the assay. Results Alkaloids in the lotus leaves were the bioactive phytochemicals and inhibited dopamine from accessing the D1 and D2 receptors. All eight compounds functioned as D1-receptor antagonists and except N-nornuciferine, seven alkaloids functioned as D2-receptor antagonists. (S)-coclaurine and (R)-coclaurine are optical isomers and antagonized both D1 and D2 with equivalent potencies, suggesting that the optical rotation of the methylene linker in the monobenzyl isoquinoline backbone did not influence their activity. Among the eight alkaloids, O-nornuciferine was the potent antagonist to both receptors (the lowest IC 50 values, D1: 2.09 ± 0.65 μM and D2: 1.14 ± 0.10 μM) while N-nornuciferine was found to be the least potent as it moderately antagonized D1 and was inactive on D2. O-nornuciferine was also a 5-HT2A antagonist (IC 50 ~20 μM) while N-nornuciferine had no activity. These hinted the importance of a methyl group attached to the nitrogen atom in the aporphine backbone. Armepavine showed a nearly 10-fold selectivity to D2. Conclusions In this work, eight alkaloids were isolated from the leaves of Nelumbo nucifera Gaertn. and assayed on the D1 and D2 receptors. They were D1/D2 antagonists with IC 50 values in the mid- to low-micromolar range and O-nornuciferine was the most potent alkaloid among the eight. This family of alkaloids was biochemically evaluated on the dopamine receptors by the same platform for the first time.
研究领域:
药理学
·
植物化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）