FOOD CHEMISTRY
·
2018
·
IF 4.946
Yike Yue,Sheng Geng,Yue Shi,Guizhao Liang,Jinshui Wang,Benguo Liu
Zein has the potential application of establishing the delivery systems for flavonoids . But there are few reports about the effect of the molecular structures of flavonoids on their interaction with zein . In this study, the binding behaviour of 21 flavonoids and zein was investigated by spectrofluorimetry. The corresponding 3D-QSAR model was also established by Topomer CoMFA method, whose steric and electrostatic field analysis could explain the binding performance of the tested flavonoids with zein. The fluorescence analysis suggested that the flavonoids could interact with zein by forming the complex at the molar ratio of 1. The flavonoids with glucosyl groups at ring A exhibited the outstanding binding capacity with zein, and their binding process with zein was driven by hydrophobic force. The synchronous and 3D fluorescence spectra showed that there was no apparent change in the microenvironment surrounding the tyrosine residues of zein during the interaction.
研究领域:
食品科学
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生物化学
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DOI
高影响因子
Food & Function
·
2020
·Vol. 11
·期 4
·3043-3052
·
IF 4.171
Wenli Yan,Guimei Lin,Rong Zhang,Zhen Liang,Wenjuan Wu
Two novel effective antioxidative tripeptides GWY and QWY were designed based on 3D-QSAR models. Their activities were confirmed by an improved TEAC assay. The experimental results showed that GWY and QWY possessed good antioxidant activity, equaling 3.32 mM TE and 2.97 mM TE respectively. This indicated that 3D-QSAR models possessed significant predictive capacity for drug design. In addition, molecular docking and molecular dynamics simulation were applied to reveal the potential molecular mechanism of antioxidant peptides. The result showed that GWY and QWY could enhance the stability of Keap1 by interacting with the key residues Arg415, Arg483, Arg380 and Ser555 in the active sites. Interestingly, the key residues were exactly the binding site of Nrf2 in the active pocket of Keap1. Thus, GWY and QWY could compete with Nrf2 for binding to Keap1. This demonstrated that the new tripeptides might have the ability to activate the signaling pathway Keap1–Nrf2–ARE and improve the antioxidant defense system of the body as well.
研究领域:
生物化学
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药物设计
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 22
·6948
·
IF 4.412
Mei Huang,Wen-Gui Duan,Gui-Shan Lin,Bao-Yu Li
A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially againstPhysalospora piricola. Compounds5b(R =o-CH3Ph),5i(R =o-Cl Ph),5v(R =m,p-OCH3Ph) and5x(R =α-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, againstP. piricola, much better than that of the positive control chlorothalonil. Compounds5v(R =m,p-OCH3Ph) and5g(R =o-Cl Ph) held inhibition rates of 82.4% and 86.5% againstCercospora arachidicolaandGibberella zeae, respectively, much better than that of the commercial fungicide chlorothalonil. Compound5b(R =o-CH3Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, againstColleterichum orbicalareandFusarium oxysporumf. sp.cucumerinum. Compounds5m(R =o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, againstF. oxysporumf. sp.cucumerinu,Bipolaris maydisandC. orbiculare. Furthermore, compound5b(R =o-CH3Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds againstP. piricola, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (r2= 0.991,q2= 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.Keywords:menthol;1,2,4-triazole-thioether;antifungal activity;3D-QSAR;molecular docking
研究领域:
药理学
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化学信息学
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真菌学
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DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 4
·e202101025
·
IF 2.745
Rong Li,Bo Cen,Wengui Duan,Guishan Lin
Succinate dehydrogenase (SDH) is an important target enzyme for designing agricultural chemical fungicides. In order to explore novel natural product-based antifungal agents, twenty-one unreported anisaldehyde-derived amide-thiourea compounds were designed and synthesized using the principle of active splicing, and structurally confirmed by 1 H-NMR, 13 C-NMR, ESI-MS, FT-IR, and element analysis. In vitro antifungal activity of the target compounds was evaluated by the agar dilution method. The results showed that some target compounds exhibited better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compounds 5c , 5o , and 5r displayed excellent antifungal activity of 92.6 %, 92.6 % and 99.1 % against P. piricola , respectively, better than that of the positive control. In addition, 3D-QSAR analysis was carried out by the CoMFA method to reveal the relationship between the structures of the target compounds and their inhibitory activities. The simulative binding mode of the target compounds and SDH was also studied by molecular docking. Graphical
研究领域:
农药化学
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分子生物学
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药物设计
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产品关联
DOI
PubMed
高影响因子
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
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2024
·
IF 2.3
Z. Ji,H. Chen,J.I. Zheng,J. Yan,H. Lu,J. He,Y. Zhu,S. Wang,L. Li,R.S. Ge,Y. Liu
Dithiocarbamate fungicides have been widely used in agricultural practices due to their effective control of fungal diseases, thereby contributing to global food security and agricultural productivity. In this study, the inhibitory potency of eight compounds on human and rat aromatase (CYP19A1) activity was evaluated. The results revealed that zineb exhibited the highest inhibitory potency on human CYP19A1 (IC50, 2.79 μM). Maneb (IC50, 3.09 μM), thiram (IC50, 4.76 μM), and ferbam (IC50, 6.04 μM) also demonstrated potent inhibition on human CYP19A1. For the rat CYP19A1, disulfiram (IC50, 1.90 μM) displayed the strongest inhibition followed by maneb (2.16 μM), zineb (2.54 μM), and thiram (6.99 μM). These dithiocarbamates acted as mixed/non-competitive inhibitors of human and rat CYP19A1. Dithiothreitol (DTT), a reducing agent, partially rescued thiram-mediated inhibition when incubated at the same. Moreover, positive correlations were observed between log P, topological polar surface area, molecular weight, and heavy atoms and IC50 values. 3D-QSAR analysis revealed the hydrogen bond acceptor and donor play critical roles in the binding of dithiocarbamates to human CYP19A1. In silico analysis showed that dithiocarbamates bind to the haem binding site, containing Cys437 residues. In conclusion, some dithiocarbamates potently inhibit human and rat CYP19A1 via interacting with haem-binding Cys437 residues.
研究领域:
药理学
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生物化学
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计算生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2023
·
IF 3.8
Hongmei Li,Guimei Lin,Zhen Liang,Ying Li,Rong Zhang
Three novel antioxidant peptides MHW, YHW and FHW were designed by the analysis of 3D-QSAR. Two accurate CoMFA ( Q 2 = 0.886 and R 2 = 0.988) and CoMSIA ( Q 2 = 0.737 and R 2 = 0.955) models were established. The FTC assay showed that activities of the new peptides on lipid peroxidation is significantly better than that of the template molecule LHW. The results of erythrocyte hemolysis assay demonstrated that MHW, YHW and FHW significantly inhibited AAPH-induced erythrocyte hemolysis by scavenging free radicals at the cellular level. It caused the restoration of intracellular antioxidant enzyme (GSH, CAT and SOD) activities at an acceptable pace and the silencing of intracellular MDA formation. Furthermore, MTT toxicity assay showed that the novel antioxidant peptides had good biocompatibility and no cytotoxicity. Molecular docking and molecular dynamics simulations were used to investigate the molecular mechanism. The results showed that Ser363, Arg380, Asn414 and Arg415 residues played key roles in the antioxidant activity of MHW, YHW and FHW. And they mainly binded to the important residues of Keap1 protein stably by electrostatic force, van der Waals force, H-bonds and hydrophobic interactions, which can better fit the Kelch pocket structural domain of Keap1. Therefore, MHW, YHW and FHW had strong potential to interfere with Keap1-Nrf2 interaction and promoted the enzymatic expression of Nrf2-ARE downstream target pathway.
研究领域:
生物化学
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药物化学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2025
·
IF 2.5
Zhuoqi Chen,Chaochao Gong,Shaowei Wang,Han Lu,Yang Zhu,Ren-shan Ge,Yunbing Tang,Yingfen Ying
Benzophenone (BP) UV-filters have been extensively used for the prevention of UV-induced adverse effects in personal care products. Their potential to interfere with steroidogenesis in the female reproductive system remains uncertain. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) facilitates the conversion of estrone to estradiol, playing a key role in estrogen activation. This study delves into the effects of eleven BPs on human and rat 17β-HSD1, while also analysing the 3D-quntitative structure-activity relationship (3D-QSAR) and the underlying mechanisms. The inhibitory potency of inhibiting human placental 17β-HSD1 was found to be in the order of BP-2 (IC 50 , 11.42 μM) > BP-1 (14.17 μM) > BP-4 (49.05 μM) > BP-6 (63.49 μM) = BP-8 (63.46 μM) > others. BP-1 and BP-2 markedly inhibited estradiol secretion by human placental BeWo cells at ≥ 1 μM. In contrast, the inhibitory strength of suppressing rat ovarian 17β-HSD1 activity was found to be in the order of BP-2 (IC 50 , 13.33 μM) > BP-1 (15.09 μM) > BP-4 (22.68 μM) > BP-12 (31.12 μM) > BP (119.99 μM) > others. Mode action analysis revealed that these BP compounds acted as mixed inhibitors of both human and rat 17β-HSD1. The introduction of a 4-hydroxyl substitution in the benzene ring was found to markedly increase the inhibitory potency against human and rat 17β-HSD1. BP-1 and BP-2 demonstrated the ability to penetrate human BeWo cells and inhibit estradiol secretion at ≥ 1 μM. Docking analysis revealed that the 2-hydroxyl group of BP-1 and BP-2 forms a hydrogen bond with catalytic residue Ser142 of human 17β-HSD1. 3D-QSAR pharmacophore analysis showed that there are hydrophobic regions and hydrogen bond donor can interact with BPs. In conclusion, this study establishes that BP-2 is the most potent inhibitors of human 17β-HSD1 among the BPs under investigation, highlighting a significant difference in the structure-activity relationship.
研究领域:
生物学
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医学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Molecular Informatics
·
2017
·Vol. 36
·期 9
·1600157
·
IF 1.955
Chunyan Qi,Guimei Lin,Rong Zhang,Wenjuan Wu
Graphical 3D-QSAR, molecular docking and activity evaluation were used to study the bioactivities of ACE-inhibitory peptides with phenylalanine C-terminus. Both CoMFA ( Q 2 =0.773, R 2 =0.992) and CoMSIA ( Q 2 =0.664, R 2 =0.990) models were constructed. According to the established models, four novel potent ACE-inhibitory tripeptides GEF, VEF, VRF, and VKF were synthesized. The IC 50 values were respectively determined to be 13 μM, 23 μM, 5 μM, and 11 μM by in vitro evaluation. The results show good agreement with the predicted values. The established models play an important role in revealing the structure-activity relationship of ACE-inhibitory peptides and designing novel peptides with enhanced biological activity.
研究领域:
药理学
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生物化学
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计算化学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Sailing Chen,Shaowei Wang,Jingyi Zheng,Han Lu,Huiqian Chen,Yunbing Tang,Nan Wang,Yang Zhu,Yiyan Wang,Ping Duan,Ren-shan Ge
Bisphenols , estrogenic endocrine-disrupting chemicals, disrupt at least one of three endocrine pathways (estrogen, androgen, and thyroid). 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is a steroidogenic enzyme that catalyzes the activation of estradiol from estrone in human placenta and rat ovary. However, whether bisphenols inhibit 17β-HSD1 and the mode of action remains unclear. This study we screened 17 bisphenols for inhibiting human 17β-HSD1 in placental microsomes and rat 17β-HSD1 in ovarian microsomes and determined 3D-quantitative structure-activity relationship (3D-QSAR) and mode of action. We observed some bisphenols with substituents were found to significantly inhibit both human and rat 17β-HSD1 with the most potent inhibition on human enzyme by bisphenol H (IC 50 = 0.90 μM) when compared to bisphenol A (IC 50 = 113.38 μM). Rat enzyme was less sensitive to the inhibition of bisphenols than human enzyme with bisphenol H (IC 50 = 32.94 μM) for rat enzyme. We observed an inverse correlation between IC 50 and hydrophobicity (expressed as Log P). Docking analysis showed that they bound steroid-binding site of 17β-HSD1. The 3D-QSAR models demonstrated that hydrophobic region, hydrophobic aromatic, ring aromatic, and hydrogen bond acceptor are key factors for the inhibition of steroid synthesis activity of 17β-HSD1.
研究领域:
分子生物学
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内分泌学
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毒理学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Qi Liu,Shan Shao,Jingyu Bao,Syed Jalil Shah,Shumin Yue,Xinqi Luan,Qing Liu,Linguang Xing,Zhongfeng Shi,Zhenxia Zhao,Zhongxing Zhao
The 3D-QSAR model is one of the most effective techniques for predicting the peptide bioactivity based on their structure properties. The accuracy of model prediction is highly dependent on the bio-activity of the peptides in its dataset. However, the same peptide used for constructing the database was reported to have obviously different activities in different published articles, which may significantly decrease the prediction accuracy. Based on this, we chose ACE inhibitory (ACE-I) dipeptides that can be absorbed directly into the human small intestine as research object. Ten dipeptides were randomly selected from the literatures for molecular docking with ACE and synthesized to test their activity. Ultimately, a linear equation was developed between bio-activities and docking scores, which was used to revalidate the reliable ACE-I activities of all reported dipeptides for constructing a credible dataset of 3D-QSAR model. The prediction accuracy was significantly enhanced and the model we established had a high Q 2 = 0.840 and R 2 = 0.998. Furthermore, dipeptide CW was predicted and tested in vitro to achieve the highest ACE-I activity (IC 50 = 0.16 μM), and the inhibition mechanism was also investigated. This study introduced a new method for predicting bio-activity with high precision using the 3D-QSAR model.
研究领域:
生物信息学
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药物化学
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生物化学
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产品关联
DOI
高影响因子
PEST MANAGEMENT SCIENCE
·
2024
·
IF 3.8
Liangliang Cheng,Cong Zhou,Qinglong Yuan,Letian Zhang,Xusheng Shao,Xiaoyong Xu,Zhong Li,Jiagao Cheng
BACKGROUND Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross-resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole β -ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D-QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half-maximal effective concentration (EC 50 ) value of 0.0398 μg mL −1 comparable to that for fluxapyroxad (EC 50 = 0.0375 μg mL −1 ), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half-maximal inhibitory concentration of 0.0425 μ m . Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen-bonds, and cation–π and π–π interactions. CONCLUSION The identified β -ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry.
研究领域:
植物保护学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Shan Shao,Huaju Sun,Yaseen Muhammad,Hong Huang,Ruimeng Wang,Shuangxi Nie,Meiyun Huang,Ziyi Zhao,Zhongxing Zhao
Efficient screening of angiotensin converting enzyme inhibitory (ACE-I) peptides from agricultural or edible sources attract increasing attention. However, their purification process from the complex natural system is still semi-empirical or even uncontrollable, which has seriously reduced their screening efficiency. Herein, inspired by the prediction of ACE-I activity, 3D-QSAR was proposed to predict the adsorption performance of peptides from sericin hydrolysate (SH) having high ACE-I activity on porous hypercross-linked polymers according to their molecular structures. Thiophene hypercross-linked polymer (T-HCP) possessing better screening capacity for ACE-I peptides was chosen as our research object in this work. The sequence and relative adsorption rate of 101 peptides in SH were analyzed by LC-MS and was used as a database to construct the relationship of peptide’s chemical structure and adsorption performance on T-HCP by Comparative molecular similarity indices analysis (CoMSIA) from 3D-QSAR. Optimum CoMSIA revealed that enhanced interaction of hydrophobicity and H-bond between T-HCP and the peptide was conducive to increase the adsorption performance of di- to hexa- peptides. Based on these relationships, the adsorption capability of 24 designed peptides with distinguished hydrophobic and H-bond fields was predicted on T-HCP by using optimum CoMSIA and the results of half of these were verified, which showed high consistency with their predicted adsorption rate. Interestingly, these peptides having higher adsorption capacities on T-HCP also possessed higher ACE-I activity. This can be attributed to the high concentration of aromatic surface with π-π interaction and weak-polar C S C group with H-bond interaction on T-HCP material, which is ideal for the selective adsorption of peptides with higher ACE-I activity from SH. This study provides important theoretical guidance for the industrial screening of bio-functional peptides from complex protein mixtures.
研究领域:
生物化学
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食品科学
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药物开发
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）