RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
·
2022
·Vol. 58
·期 10
·1520-1526
·
IF 0.862
Yang Shun,Zou Jing-Pei,Li Xiang-Rong,Li Rui,Qian Jing-Jing,Wu Wen-Long,Su Jia-Bin,Chen Ke-Qi,Qin Tian,Liu Shan-Ming,Liu Wei-Wei,Shi Da-Hua
Abstract A series of 1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated as acetylcholinesterase inhibitors. Their structure was confirmed by IR, NMR, and high-resolution mass spectra. The synthesized compounds showed significant acetylcholinesterase inhibitory activity with an IC 50 value of 0.07 μM for the most potent compound. Molecular docking study of the most active compound indicated that it interacted with the crucial amino acids present at the catalytic active site and peripheral anionic site of acetylcholinesterase. The results suggested that the obtained 1,3,4-oxadiazole derivatives may be the potential drug candidates for the treatment of Alzheimer’s disease as AChE inhibitors.
研究领域:
药物化学
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神经科学
·
有机合成
✓ 已验证
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Bei Zhang,Yi-Yi Yang,Zheng-Jiong Zhao,Run-Duo Liu,Ling-Ling Feng,Mei-Yan Jiang,Yijun Yuan,Shuheng Huang,Zhe Li,Quan Wang,Hai-Bin Luo,Yinuo Wu
Phosphodiesterase 1 (PDE1) is a subfamily of PDE super enzyme families that can hydrolyze cyclic adenosine monophosphate and cyclic guanosine monophosphate simultaneously. Currently, the number of PDE1 inhibitors is relatively few, significantly limiting their application. Herein, a novel series of quinolin-2(1H)-ones were designed rationally, leading to compound 10c with an IC50 of 15 nM against PDE1C, high selectivity across other PDEs, and remarkable safety properties. Furthermore, we used the lead compound 10c as a chemical tool to explore whether PDE1 could work as a novel potential target for the treatment of inflammatory bowel disease (IBD), a disease which is a chronic, relapsing disorder of the gastrointestinal tract inflammation lacking effective treatment. Our results showed that administration of 10c exerted significant anti-IBD effects in the dextran sodium sulfate-induced mice model and alleviated the inflammatory response, indicating that PDE1 could work as a potent target for IBD.
研究领域:
药理学
·
药物化学
·
炎症性疾病
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Gui-Li Huang,Tian-Tian Liu,Jia-Jia Ma,Ling-Xiang Sun,Si-Yao Sui,Xin-Yao Quan,Yu-Ning Wang
The harvested loquat fruits are prone to browning, leading to a decline in fruit quality. Inhibiting activity of polyphenol oxidase (PPO) is an important way to prevent browning. In this study, we evaluated the inhibitory impact of oligomeric procyanidins (OPC) on hydroxylation of monophenol and oxidation of o-diphenol catalyzed by PPO and effect of OPC on loquat fruits storage . The obtained results revealed that OPC could attenuate the activity of monophenolase and diphenolase. For monophenolase activity, the inhibition rate was observed to be dose-dependent with an IC 50 of 11.6 ± 3.4 μg/mL for the steady-state rate. For diphenolase activity, OPC inhibited PPO activity ( IC 50 = 15.75 ± 2.1 μg/mL) with a reversible and competitive mechanism and quenched fluorescence of PPO by forming OPC-PPO complex with one binding site in a static procedure. In addition, the data obtained from storage assays revealed that OPC could enhance the quality of harvested loquat fruits by attenuating the PPO activity, augmenting the content of total phenolics and flavonoids , and simultaneously delaying the browning of loquats. In this research, we identified a potent PPO inhibitor and expanded its potential as a food preservative.
研究领域:
食品科学
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植物生理学
·
采后技术
✓ 已验证
DOI
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2022
·
IF 1.097
Tiandi Ding,HaiJiao Chen,Yan Li,Ying Li,Ying Zhi,Zhiqiang Qu,Qiang Sun,Qingqiang Yao,Bo Liu
Sphingosine kinase is a lipid kinase that catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate. Sphingosine-1-phosphate is a bioactive lipid that regulates biological processes. The overexpression of sphingosine kinases is related to a variety of pathophysiological conditions. For example, SphK1 has been shown to be highly expressed in various cancer cells including ovarian, cervical, colon, stomach, lung, and brain cancer. Inhibition of sphingosine kinases is a promising way to treat diseases such as cancer. Through computer-aided drug design, we have discovered a new SphK1 inhibitor named Amb30572637 (SAMS10). In this report, we describe the discovery process and biological characteristics. In biochemical experiments, SAMS10 shows a prominent inhibitory effect on SphK1, with an IC50 value of 9.8 μM. Subsequent MTT experiments show that SAMS10 has anticancer effects toward A549, SKVO3, A375, and LOVO cell lines and has essentially no cytotoxicity against the healthy cell L929. SAMS10 has significant inhibitory activity against the A549 and LOVO cell lines, with IC50 values of 14.64 and 14.48 μM, respectively. It belongs to a moderately active SphK1 inhibitor with lower anticancer activity than the control compound cisplatin, but the effect of SAMS10 toward SphK1 and its anticancer activity indicate that it is a promising lead compound for the development of effective SphK1 anticancer inhibitors.
研究领域:
药理学
·
癌症研究
·
药物发现
·
生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Yong Guo,Enhua Hou,Nannan Ma,Zhiyan Liu,Jiangping Fan,Ruige Yang
Nowadays, the discovery and development of α -glucosidase inhibitors from natural products or their derivatives represents an attractive approach. Here we reported studies on a series of novel N -acyl-2-aminothiazoles fused (+)-nootkatone and evaluation for their α -glucosidase inhibitory activities. Most of (+)-nootkatone derivatives exhibited more potent α -glucosidase inhibitory ability than the positive drug acarbose. In particular, compounds II7 and II14 showed the most promising α -glucosidase inhibitory ability with IC 50 values of 13.2 and 13.8 µM. II7 and II14 also exhibited relatively low cytotoxicities towards normal LO2 cells. Kinetic study indicated that compounds II7 and II14 inhibited the α -glucosidase in a noncompetitive manner, and molecular docking results were in line with the noncompetitive characteristics that II7 and II14 did not bind to the known active sites (Asp214, Glu276 and Asp349). Based on our findings, these (+)-nootkatone derivatives could be used as antidiabetic candidates.
研究领域:
药理学
·
药物化学
·
天然产物
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2024
·
IF 3.2
Hao-Dong Yang,Yuan-Gui Yang,Zhi-Shu Tang,Kang Ma,Hong-Bo Xu
Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans ( 1 – 4 ) and 12 known lignans ( 5 – 16 ) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1 – 16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1 – 16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2 , 6 – 8 and 13 – 16 demonstrate better COX-2 inhibitory effects with IC 50 values from 0.75 to 8.17 μ Μ. These findings provide useful information for the search for natural selective COX-2 inhibitors.
研究领域:
药理学
·
中药学
·
天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Tongmei Shi,Jieling Lin,Shiyun Liang,Yu Song,Xin Zhao,Mengjie Xiao,Huihui Ti
A B S T R A C T Headings ethnopharmacological relevance Sangbaipi Decoction (SBPD) is an effective treatment for lung diseases caused by phlegm-heat obstruction according to Jingyue Quanshu , and soothes panting by purging the lung meridian. It is composed of anti-pyretic herbs (e.g., Scutellaria baicalensis Georgi and Coptis chinensis Franch.) and antitussive herbs (e.g., Cortex Mori and Armeniacae Semen Amarum ). Therefore, we hypothesized that SBPD has therapeutic effects on lung injury caused by influenza virus. Aim of the study This study aimed to explore anti-influenza activity, active components, and mechanisms of SBPD. Materials and methods The anti-influenza activities of SBPD were determined in 48 h drug-treated MDCK cell model using CPE and plaque reduction assays, and 24 h drug-treated A549 cells using qRT-PCR. The in vivo efficacy of SBPD (1.0g/kg/day and 0.5g/kg/day) was evaluated in PR8 infected BALB/c mice. The chemical component was assessed through HPLC-Q-TOF MS/MS analysis. Network pharmacology was built via TCMSP, GeneCards, DisgeNet, OMIM, DrugBank databases, and Cytoscape software. Additionally, TOA, HI and NAI assays were employed to investigate impact on the virus replication cycle with different concentrations of SBPD (2.5 mg/mL, 1.25 mg/mL, or 0.625 mg/mL). Results In MDCK infected with viruses A/PR/8/34, A/Hong Kong/1/68, or A/California/4/2009, the IC 50 values of SBPD were 0.80 mg/mL, 1.20 mg/mL, and 1.25 mg/mL. In A549 cells, SBPD treatment reduced cytokine expression (e.g., TNF-α, IL-6, IL-1β) ( p < 0.05). In PR8 infected BALB/c mice, SBPD improved the survival rate of infected mice, reduced lung index ( p < 0.05), protected lung tissue from pathological damage, and regulated cytokine overexpression ( p < 0.05). 29 components of SBPD were identified in SBPD treated mouse serum including some phytochemicals targeting influenza proteins. HI and NAI assays suggested the potential antiviral mechanism of SBPD through inhibition of HA and NA. Conclusion This study is the first to demonstrate the anti-influenza and the anti-inflammatory effects of SBPD in vitro and in vivo. Its major anti-influenza phytochemicals were explored and its inhibitory effects on HA and NA protein were proved. It provides more options for anti-influenza drug discovery.
研究领域:
药理学
·
病毒学
·
中医
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2014
·
IF 6.451
Huanshun Yin,Xinxu Wang,Yunlong Guo,Yunlei Zhou,Shiyun Ai
An effective assay method for monitoring protein kinase activity and screening inhibitors is greatly beneficial to kinase-related drug discovery, early diagnosis of diseases, and therapeutic effect evaluation. Herein, we develop a simple electrochemical method for detecting the activity of casein kinase II (CK2) based on phosphorylation against carboxypeptidase Y (CPY) digestion triggered signal amplification , where CK2 catalyzed phosphorylation event protects the substrate peptide from the digestion of CPY, maintains the repulsive force of the substrate peptide towards the redox probe, and results in a weak electrochemical signal. Whereas, without phosphorylation, the substrate peptide is digested by CPY and a strong electrochemical signal is obtained. The detection feasibility is demonstrated for the assay of CK2 activity with low detection limit of 0.047 unit/mL. Moreover, the biosensor was used for the analysis of kinase inhibition. Based on the electrochemical signal dependent inhibitor concentration, the IC 50 value of ellagic acid was estimated to be 39.77 nM. The proposed method is also successfully applied to analyze CK2 activity in cell lysates, proving the applicability in complex biological samples.
研究领域:
生物化学
·
分析化学
·
药物发现
·
疾病诊断
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Bingzhi Li,Lei Xu,Yue Chen,Wanying Zhu,Xin Shen,Chunhong Zhu,Jieping Luo,Xiaoxu Li,Junli Hong,Xuemin Zhou
Transcription factors (TFs) regulate gene expression by binding to regulatory regions, and their dysregulation is involved in numerous diseases. Thus, they are therapeutic targets and potential diagnostic markers. However, widely used methods for TFs detection are either cumbersome or costly. Herein, we first applied DNA-Ag nanoclusters molecular beacons (AgMBs) in TFs analysis and designed an assay based on the switchable fluorescence of AgMBs. In the absence of TFs, a single-stranded DNA functioned as a reporter is released from a double-stranded DNA probe (referred as dsTFs probe) under exonuclease III (Exo III) digestion. Then, the reporter triggers downstream Exo III-assisted signal amplification by continuously consuming the guanine-rich enhancer sequences in AgMBs, resulting in significant fluorescent decrease eventually. Conversely, the presence of TFs protects the dsTFs probe from digestion and blocks the downstream reaction to keep a highly fluorescent state. To testify this rationale, we utilized nuclear factor-kappa B p50 (NF-κB p50) as a model TFs. Owing to the amplification strategy, this method exhibited high sensitivity toward NF-κB p50 with a limit of detection of 10 pM, and a broad linear range from 30 pM to 1.5 nM. Furthermore, this method could detect multiple TFs in human colon cancer DLD-1 cells and reflect the variation in their cellular levels after stimulation. Finally, by conducting an inhibition assay we revealed the potential of this method for screening TFs-targeted drugs and calculating the IC50 of corresponding inhibitors.
研究领域:
生物化学
·
分子生物学
·
生物技术
·
癌症研究
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2018
·
IF 3.185
Yu-Feng Shen,Lei Liu,Chen-Zhang Feng,Yang Hu,Cheng Chen,Gao-Xue Wang,Bin Zhu
Coumarin as a lead structure have received a considerable attention in the last three decades for the discovery of antiviral agents. Our previous study indicated that imidazole coumarins possessed antiviral activities against SVCV . Based on the structure-activity relationship in that study, a new imidazole coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), was designed, synthesized and its anti-SVCV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BBC (IC 50 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole coumarins in our previous study. Besides, BBC can significantly inhibit cell death and reduce cellular morphological damage induced by SVCV. Our further data indicated that intraperitoneal injection of BBC increased the survival rate of zebrafish by 17.5%, decreased viral titer in fish body and inhibited SVCV glycoprotein expression in kidney and spleen . In uninfected zebrafish, the expression levels of ifnγ , ifnφ1 , ifnφ2 and rig1 genes were up-regulated after BBC treatment, which indicated that BBC could activate interferon response. In addition, data of the antioxidant enzymes activities and results of the antioxidant enzymes-related genes expressions suggested BBC could reduce SVCV-induced oxidative damage in infected zebrafish. Altogether, BBC is expected to be a therapeutic agent against SVCV infection in the field of aquaculture.
研究领域:
水产养殖
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2014
·
IF 3.84
Yunlei Zhou,Mo Wang,Zhiqing Yang,Huanshun Yin,Shiyun Ai
A novel, sensitive and label-free photoelectrochemical assay for monitoring the activity and inhibition of protein kinase A (PKA) was presented based on the specific recognition ability of biotinylated Phos-tag for kinase-induced phosphopeptides. When the assembled substrate peptides were phosphorylated by PKA, they could bind specifically to the biotinylated Phos-tag in the presence of Zn 2+ . Then streptavidins could be further captured on the electrode surface through their specific interaction towards biotin, resulting in a significant decrease on the photocurrent of substrate Bi 2 S 3 modified ITO electrode. The decreased photocurrent was proportional to the PKA concentration ranging from 0.05 to 100 unit/mL with a detection limit of 0.017 unit/mL ( S / N = 3). Moreover, this photoelectrochemical method could be also used to quantitative analysis of kinase inhibition. In the light of the inhibitor concentration dependant photocurrent signal, the IC 50 value for ellagic acid and HA-1077 was estimated to be 3.23 and 1.77 μM, respectively. With changing the sequence of substrate peptide, this method could also be applied to detect other kinase activity and inhibitors. Therefore, the developed protocol provides a new and promising platform for assay of kinase activity and its inhibitors with low cost and high sensitivity.
研究领域:
生物化学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
STARCH-STARKE
·
2023
·
IF 2.3
Yao Wen,Caimei Su
A Box–Behnken design (BBD) of response surface methodology (RSM) is employed to further optimize ultrasonic-assisted extraction conditions for Ophiopogon japonicus polysaccharides. The results show that optimized extraction conditions are liquid–solid ratio of 22:1 mL g −1 , ultrasonic time of 27 min, and ultrasonic power of 200 W. Under these conditions, the mean experimental value of extraction yield (39.49%) is achieved, which is 1.33 times that of distilled water leaching extraction (29.68%). In addition, one of the eluting fractions, SPs-1 , has high α -glucosidase and α -amylase inhibitory activities as well as 1,1-Diphenyl-2-picrylhdrazyl radical and α-glucosidase, 2,2’-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) cation scavenging activities with an IC 50 value of 0.060, 0.021, 0.50, and 0.10 mg mL −1 . Therefore, SPs-1 from O. japonicus can be considered as multifunctional biological ingredients to be used in anti-hyperglycemic pharmaceutical formulation and antioxidant in functional foods.
研究领域:
药学
·
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）