Food & Function
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2020
·Vol. 11
·期 4
·3043-3052
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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
PROCESS BIOCHEMISTRY
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2023
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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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Feng Hao,Wenxuan Wu,Kaida Li,Huawen Wang,Xiaoyan Zhou,Liyun Jiang,Jiting Li,Zhongtao Ding,Le Cai
The escalating global population and the resulting increase in food demand have been met with growing challenges from pest infestations, particularly lepidopteran pests, which significantly damage crops. Traditional chemical insecticides face issues such as the development of resistance and environmental harm. Therefore, there is an urgent need for the development of novel insecticides. Sulfone compounds, widely recognized for their utility in medicinal chemistry, have demonstrated potential in enhancing insecticidal efficacy while mitigating environmental impacts. In this study, we explored the design and synthesis of a novel series of sulfone compounds through scaffold hopping strategy and the principle of bioelectronics with the aim of improving insecticidal efficacy against key pests such as Spodoptera litura, Spodoptera frugiperda, and Spodoptera exigua. After evaluating the larvicidal activities, compounds W-27 (LC50 = 0.1205 mg/L) and W-29 (LC50 = 0.1262 mg/L) have emerged as standout performers, exhibiting outstanding larvicidal activity that not only meets but exceeds the potency of the positive control fluralaner (LC50 = 0.1862 mg/L). Structure–activity relationship (SAR) analysis and molecular docking studies were conducted to explore the mechanisms underlying their activity. Additionally, a 3D-QSAR model was developed to predict the insecticidal potency of novel compounds. Toxicity testing on nontarget organisms, such as Solanum lycopersicum and Danio rerio, further confirmed the environmental safety of these compounds. This study paves the way for the development of a new class of agrochemicals, offering novel scaffolds for future pest control applications.
研究领域:
农业化学
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药物设计
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害虫控制
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2025
·
IF 4.7
Ya-Kun Zhang,Jian-Bo Tong,Hong-Yan Zhang,Mu-Xuan Luo,Zhi-Peng Qing,Cheng-Jian Tan
Topoisomerase I (Top I) plays a pivotal role in resolving DNA supercoiling during replication and transcription, highlighting its significance as a therapeutic target in oncology. Despite the clinical efficacy of inhibitors such as Irinotecan and Topotecan, their clinical utility is hindered by the emergence of resistance mechanisms. Sophoridine, a natural alkaloid, has demonstrated promising Top I inhibitory activity, with its derivatives showing enhanced antitumor effects. In this study, the Topomer CoMFA approach was utilized to construct a validated 3D-QSAR model to explore the structure-activity relationships (SAR) of sophoridine derivatives. Based on the model's guidance, nine derivatives were designed, four of which were synthesized and subjected to biological evaluation. Computational investigations, including molecular docking, molecular dynamics simulations, and ADMET predictions, provided detailed insights into their binding interactions and drug-like properties. These findings establish a robust theoretical framework for the rational design of sophoridine-based Top I inhibitors with potential applications in cancer treatment.
研究领域:
药理学
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计算化学
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肿瘤学
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产品关联
DOI
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
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DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2024
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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
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