MOLECULES
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2021
·Vol. 26
·期 14
·4361
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IF 4.412
Ya Wang,Xiao-Jing Shen,Fa-Wu Su,Yin-Rong Xie,Li-Xia Wang,Ning Zhang,Yi-Long Wu,Yun Niu,Dong-Ying Zhang,Cheng-Ting Zi,Xuan-Jun Wang,Jun Sheng
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds11and12showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50values in the range of 22.90–37.87 μM. Compounds11and12decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds11and12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.Keywords:EGCG;synthesis;cytotoxicity;EGFR;molecular docking
研究领域:
药理学
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肿瘤学
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化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2025
·
IF 5.1
Yudong Su,Jinman Shui,Danshi Qi,Jie Bai,Xiaoxia Xu,Yongchun Huang,Ruilian Li,Qiong Wu,Haiyan Wang,Chengzhu Cao,Zhanhai Su,Shoude Zhang
Purpose Erectile dysfunction (ED), a prevalent form of male sexual dysfunction, is predominantly treated with Phosphodiesterase type 5 inhibitors (PDE5Is). Our previous research highlighted procyanidin, a natural compound, as a notably effective PDE5I. In the current study, we intend to further validate the inhibitory activity of procyanidin on PDE5A through in vitro and in vivo assessments. This study aims to validate the efficacy of procyanidin as a treatment for ED.Methods The binding affinity of procyanidin for PDE5A was assessed by molecular docking, molecular dynamics (MD) simulations, and microscale thermophoresis (MST) assay. The toxicity of procyanidin on penile corpus cavernosum smooth muscle (CCSM) cells (n=5) was evaluated. Additionally, its effects on intracellular cyclic guanosine monophosphate (cGMP) levels in CCSM cells (n=5) were evaluated. The absorption of procyanidin was evaluated by measuring plasma levels at various times after oral gavage to Sprague-Dawley (SD) rats (n=6). Subsequently, the effects of procyanidin on intracavernous pressure (ICP) and cGMP levels in penile cavernous tissue were evaluated in SD rats (n=6).Results Procyanidin forms three hydrogen bonds with PDE5A and stabilizes the complex structure, exhibiting equilibrium dissociation constants (KD) value of 7.77 ± 2.39 µmol/L. Additionally, procyanidin exhibits minimal cytotoxicity toward CCSM cells and significantly elevates intracellular cGMP levels compared to the control group. In vivo studies demonstrate that procyanidin is rapidly absorbed, achieving peak blood concentrations within one hour. Simultaneously, procyanidin significantly increases ICP and cGMP levels in rats compared to the control group.Conclusion These findings indicate that procyanidin sustains elevated cGMP levels within cells by targeting PDE5A, thereby exhibiting therapeutic efficacy in improving ICP. Procyanidin emerges as a promising PDE5I for treating ED and potentially other related conditions.
研究领域:
药理学
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泌尿学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
SOUTH AFRICAN JOURNAL OF BOTANY
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2023
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IF 3.1
Hui Li,Keren Agyekumwaa Addo,Yi-gang Yu,Xing-long Xiao
In Iranian, ethnopharmacological studies show that Cuminum cyminum is commonly used in pain relief. The most abundant component in C. cyminum seeds is cuminaldehyde (CUM). However, there are few articles that have evaluated the anti-biofilm activity against Staphylococcus aureus ( S. aureus ). The nobility of this study was to evaluate the anti-biofilm effect of CUM and to investigate its possible mechanism of action. Crystal violet staining assay showed that CUM decreased biofilm biomass. The morphological observation indicated that CUM restrained the adhesion of biofilm, and destroyed the integrated and cohesive structure of biofilm. MTT assay proved that the metabolic activity of adherent cells treated with CUM was reduced. In vitro assays exhibited that cell motility, cell surface hydrophobicity, and extracellular polymers production of S. aureus were also inhibited in the presence of CUM. Furthermore, quantitative real-time PCR analysis confirmed the ability of CUM to interfere with the expression of adhesion genes associated with biofilm formation such as agrA, icaA, sigB, ebpS, fnbA, fib and clfA . Molecular docking speculated that the interaction of CUM with SarA could inhibit SarA-DNA binding, and ultimately inhibit the formation of biofilm. The results of this trial provided scientific experimental data for the use of CUM as an anti-biofilm agent.
研究领域:
微生物学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
·
IF 4
Shiling Liu,Siying Qin,Tengfei Zhang,Heng Zhang,Junqi Zhu,Xiaoli Li,Yuanfu Li,Feng Zhao
Flusulfinam is a novel chiral amide herbicide widely used for controlling annual weeds in rice paddies. However, the mechanism underlying their enantioselective herbicidal activity remain unclear. Herein, it was found that flusulfinam enantiomers, similar to typical HPPD inhibitor mesotrione, reduced chlorophyll a nd carotenoid levels, decreased HPPD enzyme activity, and upregulated gene expression. Additionally, homogentisate supplementation alleviated the bleaching symptoms caused by flusulfinam and all these results validate that flusulfinam is indeed an HPPD inhibitor. To further investigate the mechanism of enantioselectivity, molecular docking was used and showed that R -flusulfinam (−6.55 kcal/mol) had higher binding energy than S- flusulfinam (−5.60 kcal/mol), due to more stable hydrogen bonds with Gln293. After mutating Gln293 to His, the IC 50 values for R -flusulfinam and S -flusulfinam on Mut Q293H were 0.73 mg/L and 0.11 mg/L, respectively, indicating swapped enantioselective inhibition compared to At HPPD, with IC 50 values of 0.52 mg/L and 1.93 mg/L, respectively. The Microscale Thermophoresis assay further revealed that the dissociation constant (Kd) for Mut Q293H with R -flusulfinam was 20.40 ± 4.19 μM, similar to the Kd value of 15.63 ± 4.51 μM for S -flusulfinam. The findings reveal that mutation of the Gln293 residue in the At HPPD enzyme significantly altered its enantioselective inhibition by flusulfinam. This study is the first to verify the mode of action of flusulfinam and identifies that Gln293 may play a key role in flusulfinam enantioselectivity in the At HPPD, laying the foundation for future HPPD inhibitor development based on flusulfinam.
研究领域:
植物生理学
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分子生物学
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农药科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ping Li,Changchang Wang,Gun Chen,Yixiao Han,Hanyu Lu,Nan Li,Yangbin Lv,Chu Chu,Xin Peng
Ethnopharmacological relevance Tetrastigma hemsleyanum （ T. hemsleyanum ）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. Aim of the study To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. Materials and methods The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI–H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum . Results We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI–H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum , such as procyanidin B1, catechin , quercetin , and kaempferol , etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7 , respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. Conclusion In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum , which further consolidated the claim of its traditional uses.
研究领域:
药理学
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生物信息学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2019
·
IF 2.12
Xiaopei Wang,Yuanyuan Yue,Yanyan Zhang,Zhiyue Wang,Jianming Liu,Qinghu Tang
The use of the pesticide imidacloprid can be hazardous to human health. In this work, the impacts of imidacloprid on the secondary structure of pepsin were investigated through spectroscopic techniques and simulation studies. One binding site for pepsin with strong affinity was evident from changes in the fluorescence emission spectra of pepsin in the presence of imidacloprid. Calculated thermodynamic parameters based on the van't Hoff relationship indicate the predominance of hydrophobic and hydrogen bonding interactions contributing to the imidacloprid-pepsin complex. Structural changes in pepsin were also evident from changes in the UV, FTIR , CD , three-dimensional fluorescence (3D), and synchronous fluorescence spectroscopy (SFS) of pepsin upon titration with imidacloprid. Furthermore, density functional theory (DFT) calculations and molecular docking studies revealed predominant binding of imidacloprid in the hydrophobic pocket of pepsin.
研究领域:
生物化学
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毒理学
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计算生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Ming Ying,Manjunath D. Meti,Hong Xu,Yuhan Wang,Jialiang Lin,Zhibing Wu,Qingguo Han,Xu Xu,Zhendan He,Wenxu Hong,Zhangli Hu
The interaction of lipase with Ligupurpuroside B was studied by multiple spectroscopic techniques , enzyme activity and molecular modeling under simulative physiological condition. According to Stern-Volmer equation, fluorescence of lipase was quenched by Ligupurpuroside B via a static quenching mechanism because of formation of Ligupurpuroside B-lipase complex. Binding constants , number of binding sites & thermodynamic parameters were evaluated. The values of Δ G o (−25.085 kJ mol −1 ), Δ H o (−12.14 kJ mol −1 ) and Δ S o (+43.45 J mol −1 K −1 ) at 298 K indicated that Ligupurpuroside B-lipase interaction is spontaneous and hydrophobic interaction is the main force stabilizing the Ligupurpuroside B-lipase complex. The enzyme activity assay showed that Ligupurpuroside B inhibited lipase activity efficiently. Synchronous fluorescence spectra (SFS) suggested that Ligupurpuroside B is closer to Trp residues than to Tyr residues. All above experimental results were confirmed by molecular docking studies, which further indicated the binding site of Ligupurpuroside B on the surface of lipase, and the amino acid residues of lipase interacting with Ligupurpuroside B. Our present research work gives valuable information on the design of drugs with lipase as a carrier and should be useful for food industries.
研究领域:
生物化学
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药物设计
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食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2024
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IF 4.2
Zhe-Ran Wu,Yi-Wen Pei,Xiao-Qing Zhang,Min Lu,Xiao-Long Liu
Chemical sensing systems are vital in the growth and development of insects. Orius sauteri (Poppius) (Hemiptera: Anthocoridae) is an important natural enemy of many pests. The molecular mechanism of odorant binding proteins (OBPs) binding with common insecticides is still unknow in O. sauteri . In this study, we expressed in vitro OsauOBP8 and conducted fluorescence competition binding assay to investigate the function of OsauOBP8 to insecticides. The results showed that OsauOBP8 could bind with four common insecticides (phoxim, fenitrothion, chlorpyrifos, deltamethrin). Subsequently, we used molecular docking to predict and obtained candidate six amino acid residues (K4, K6, K13, R31, K49, K55) and then mutated. The result showed that three key residues (K4, K6, R31) play important role in OsauOBP8 bound to insecticides. Our study identified the key binding sites of OsauOBP8 to insecticides and help to better understand the molecular mechanism of OBPs to insecticides in O. sauteri .
研究领域:
昆虫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Chemistry-X
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2024
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IF 6.5
Maiquan Li,Yunxia Dong,Mangjun Kang,Tiantian Tao,Wenlan Li,Sheng Zhang,Wei Quan,Zhonghua Liu
Hyperglycemia can cause early damage to human bady and develop into diabates that will severely threaten human healthy. The effectively clinical treatment of hyperglycemiais is by inhibiting the activity of α-amylase. Black tea has been reported to show inhibitory effect on α-amylase and can be used for hyperglycemia treatment. However, the mechanism underlying is unclear. In this study, in vivo experiment showed that black tea theaflavins extract (BTE) effectively alleviated hyperglycemia. In vitro experiment showed that the effects may be caused by the interation between theaflavins and α-amylase. While TF1 and TF3 were mixed type inhibitors of α-amylase, TF2A and TF2B were competitive inhibitors of α-amylase. Molecular docking analysis showed that theaflavins monomers interacted with the hydrophobic region of α-amylase. Further study verified that monomer-α-amylase complex was spontaneously formed depending on hydrophobic interactions. Taken together, theaflavins showed potential anti-hyperglycemia effect via inhibiting α-amylase activity. Our results suggested that theaflavins might be utilized as a new type of α-amylase inhibitor to prevent and cure hyperglycemia.
研究领域:
营养学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 5
·581
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IF 4.8
Jiaming Cao,Boyuan Xiang,Baojie Dou,Jingfei Hu,Lei Zhang,Xinxin Kang,Mingsheng Lyu,Shujun Wang
Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation ofTrichiurus lepturus(ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50= 262.98 μM), QGPIGPR (IC50= 81.09 μM), and GPTGPAGP (IC50= 168.11 μM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.
研究领域:
食品科学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2020
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IF 3.232
Fengmao Li,Yunming Tang
Peroxidase , a key enzyme causing enzymatic browning, and affected the potential values of fruit and vegetables. Phytic acid and NADH inhibited peroxidase in a competitive manner due to their reducing properties, and it's IC 50 (1.18 ± 0.32) × 10 −8 , (8.02 ± 0.45) × 10 −6 mol L −1 , respectively. The interaction between phytic acid, NADH and peroxidase contributed to intrinsic fluorescence quenching and conformation alternation with a accuracy determination by multispectroscopic techniques (fluorescence spectra, FT-IR and CD spectra), respectively. Molecular docking simulation revealed that phytic acid, NADH interacted with His170, Ala34, Arg38, Ser73, Arg31, Lys174, Gln176, Asn175, Arg75; Gln176, Asn175, Phe221, Lys174, Gly173, Ser167, Phe172, Gly169, His170 in peroxidase, respectively and blocked substrates into catalytic reactions.
研究领域:
食品科学
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生物化学
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植物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxins
·
2019
·Vol. 11
·期 9
·497
·
IF 3.895
Zhi-Zhen Pan,Lian Xu,Yi-Shu Zheng,Li-Yang Niu,Bo Liu,Yan Shi,Qing-Xi Chen,Yu-Jing Zhu,Xiong Guan
Bacillus thuringiensisinsecticidal proteins (Bt toxins) have been widely used in crops for agricultural pest management and to reduce the use of chemical insecticides. Here, we have engineered Bt toxin Cry2Ab30 and bioconjugated it with 4”-O-succinyl avermectin (AVM) to synthesize Cry2Ab–AVM bioconjugate. It was found that Cry2Ab–AVM showed higher insecticidal activity againstPlutella xylostella, up to 154.4 times compared to Cry2Ab30. The binding results showed that Cry2Ab–AVM binds to the cadherin-like binding protein fragments, the 10th and 11th cadherin repeat domains in theP. xylostellacadherin (PxCR10–11), with a much higher affinity (dissociation equilibrium constantKD= 3.44 nM) than Cry2Ab30 (KD= 28.7 nM). Molecular docking suggested that the macrolide lactone group of Cry2Ab–AVM ligand docking into the PxCR10–11is a potential mechanism to enhance the binding affinity of Cry2Ab–AVM to PxCR10–11. These findings offer scope for the engineering of Bt toxins by bioconjugation for improved pest management.Keywords:Cry2Ab–AVM bioconjugate;binding affinity;molecular dockingKey Contribution:The study develops an engineered Cry2Ab by bioconjugation with 4”-O-succinyl avermectin to enhance insecticidal potency againstP. xylostella.This engineering also improves its affinity to the cadherin-like binding fragments. Homology modeling and docking study are also carried out to investigate the binding model.
研究领域:
农业生物学
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昆虫学
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蛋白质工程
✓ 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）