TOXICOLOGY IN VITRO
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2021
·
IF 3.5
Shuyu Ouyang,Dachuan Zhang,Tengfei Zhu,Shuting Yu,Wunier,Qian-Nan Hu,Yingying Le
β 2 -adrenoceptor (β 2 AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through β 2 AR. The activity of 25 β 2 AR agonist s was measured by β 2 AR-cAMP response element (CRE) –luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R 2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of β 2 AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of β 2 AR agonists in activating the β 2 AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.
研究领域:
药理学
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分子生物学
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生物信息学
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毒理学
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高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Yongle Yu,Lin Zhu,Yenong Shi,Haowen Tong,Jamal A.H. Kowah,Lisheng Wang,Xu Liu
In this study, three-dimensional quantitative conformational relationship (3D-QSAR) analysis was conducted on 38 known anthraquinone derivatives. Additionally, five pH-responsive anthraquinone photosensitizers ( A1 to A5 ) were designed and synthesized through addition, elimination, and substitution mechanisms using the anthraquinone derivative chrysophanol as the raw material. The structures of the products were characterized using 1 HNMR, 13 CNMR , LCMS, and the UV–Vis absorption spectra and fluorescent spectra at different pH values were obtained. To investigate the photodynamic antibacterial activity of the compounds, their inhibitory activities against Pseudomonas aeruginosa and Staphylococcus aureus were tested in vitro under different light and pH conditions. The results showed that the compounds exhibited good photodynamic antibacterial activity and selectivity in light and weak acid environments. MTT experiments were conducted to evaluate the cytotoxicity of the compounds on the human cancer cell line HeLa. It was found that the phototoxicity and dark toxicity effects of compound A3 at concentrations of 0.625 μM and lower were similar to those of the reference photosensitizer Chlorin e6 (Ce6). However, the amount of singlet oxygen produced by A3 was approximately 7.6 times that produced by Ce6, indicating its potential for application in the photodynamic therapy of tumours and providing a reference for research on anthraquinone photosensitizers.
研究领域:
药物化学
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光化学
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微生物学
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癌症研究
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生物化学
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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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PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-13
·
IF 5.228
Fang Yajing,Lu Yulin,Zang Xixi,Wu Ting,Qi XiaoJuan,Pan Siyi,Xu Xiaoyun
Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti- Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC 50 values of flavonoids. The cross-validated coefficient ( q 2 ) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents.
研究领域:
药物化学
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微生物学
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计算化学
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结构生物学
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药学
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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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高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2024
·
IF 5.3
Guilan Jiang,Silin Li,Jingyi Zhu,Binbin Li,Zhuhong Ding
To investigate the conformational relationship and mechanism of action of β-glucosidase (BGL) activators, a theoretical study of three-dimensional quantitative structure activity relationship, molecular docking, molecular dynamics (MD) simulations, and binding free energy analysis were performed. The results indicate that comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models had good stability and predictive ability, with r 2 cv / r 2 pred values of 0.540/0.998 and 0.654/0.993, respectively. The derived contour maps of steric, electrostatic, and hydrogen bond donor field further displayed the modified information of these activators. Molecular docking and MD were performed on calcium diascorbate (CaAS) and L-Ascorbyl 2,6-Dipalmitate (L-ADP), which have good activating ability. The study indicates a positive interaction between the activators and the enzyme, and this interaction does not cause irreversible negative effects on the conformation of BGL. The MD results show that the total binding free energies of CaAS and L-ADP with BGL were −19.837 kJ/mol and −37.798 kJ/mol, respectively, and the binding force of the activators with BGL was mainly derived from hydrophobic interaction and hydrogen bonding. This study offers important guidance for the efficient use of BGL and for the research and development of effective activators.
研究领域:
生物化学
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药物化学
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计算化学
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酶学
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DOI
高影响因子
RSC Advances
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2016
·Vol. 6
·期 56
·50837-50845
·
IF 3.289
Bin Liu,Ji-Mei Ma,Hang-Wei Chen,Zi-Long Li,Lin-Hao Sun,Zhen Zeng,Hong Jiang
α-Glucosidase inhibitors can effectively control postprandial hyperglycemia. In this study, a series of phenolic acids with the L-amino acid moiety were synthesized and their inhibitory activities against α-glucosidase from Saccharomyces cerevisiae (EC 3.2.1.20) were evaluated. The results suggested that all these compounds showed strong α-glucosidase inhibitory activities. In particular, N-(4-hydroxyl-phenylpropenoyl)-L-alanine (c2) and N-(4-hydroxyl-phenylpropenoyl)-L-methionine (c8) exhibited much higher potency (IC50 values 0.04 mM) than the positive control, acarbose (IC50 values 1.70 mM). Three-dimensional quantitative structure–activity relationship (3D-QSAR) model for comparative molecular field analysis (CoMFA) was generated and the result showed that bulk groups and high electron density groups on the amino acid residues were a benefit to their activities. Moreover, the substituents with low electron density and little steric hindrance on the para position of the benzene ring were helpful in improving the activities. Kinetic analysis indicated that compound (c2) acted as a mixed-type inhibitor with a Ki value of 0.0124 mM. Docking analysis showed that they could bind to α-glucosidase at the catalytic site via hydrogen bonds and a π–π stacking.
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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DOI
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 7
·1078
·
IF 5.1
Yao Chen,Yu-Cheng Cui,You-Qiong Bi,Zhang-Li Guo,Xian-Li Ma,Wen-Gui Duan,Gui-Shan Lin
In order to find green fungicides derived from natural products, 22 unreported anethole-based thiazolinone-hydrazone compounds were designed and synthesized, and their structures were characterized by FT-IR,1H NMR,13C NMR, and HRMS. At a concentration of 50 mg/L, the preliminary antifungal activity of the target compounds against eight plant pathogens was evaluated. The results showed that5q(R =m-OH C6H4) exhibited the best inhibitory activity against most of the tested plant pathogenic fungi, demonstrating that this compound had certain broad-spectrum antifungal activity. In addition, a reasonable and effective 3D-QSAR model (r2= 0.994,q2= 0.529) was established using the comparative molecular field analysis (CoMFA) method to study the relationship between the structures of the target compounds and their antifungal activity againstPhysalospora piricola. Meanwhile, the results of electrostatic potential calculation of the compounds indicated that the electronic effect caused by different substituents on the benzene ring might be one of the factors affecting antifungal activity. In addition, frontier molecular orbital calculations implied that the anethole moiety and the thiazolinone-hydrazone-benzene structure in the target compounds might play an important role in antifungal activity. The potential binding mode between the target compound5q(R =m-OH C6H4) and the homology-modeled succinic dehydrogenase was explored by molecular docking.
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FOOD RESEARCH INTERNATIONAL
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2022
·
IF 7.425
Yuandong Yu,Guizhao Liang,Huabin Wang
Tartary buckwheat bran protein (TBBP) is a valuable by-product of Tartary buckwheat processing. Current studies have indicated that TBBP is a desirable carrier and protector of flavonoids. However, the quantitative structure-affinity relationship of flavonoids with TBBP still remains to be elucidated. Here, by using the fluorescence spectroscopy method to measure the binding constants of 16 flavonoids with TBBP, we employ a combination of the atom-based three dimensional-quantitative structure-affinity relationships (3D-QSAR) and quantum-chemical calculation to explore the underlying binding mechanisms. We show that flavonoids can cause the intrinsic fluorescence quenching and form non-covalent complexes with TBBP driven by hydrogen bonding and van der Waal forces. The atom-based 3D-QSAR model reveals that the rutoside group at the C-7 position of flavones is favorable to enhance the binding constants of flavonoids with TBBP. Quantum-chemical calculations consistently disclose that the rutoside group can intensify interaction forces of flavonoids, thereby strengthening the binding. This work provides theoretical evidence that TBBP has the potential application to be raw materials for develop functional food, and be the delivery carriers of flavonoids.
研究领域:
食品科学
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分子营养学
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生物物理化学
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功能食品
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药物传递
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天然产物化学
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蛋白质-配体相互作用
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高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Sheng Geng,Guoyang Liu,Lu Bai,Chunyan Wang,Wei Yang,Yangyang Jia,Huan Liu,Benguo Liu
This research elucidates the mechanisms of non-covalent interactions between flavonoids and lysozyme. Binding constants were determined via fluorescence spectroscopy, and a Topomer CoMFA 3D-QSAR model was developed, effectively explaining the binding behavior. Detailed studies on rutin, naringenin, and hesperetin showed binding occurred via a static quenching mechanism with a 1:1 stoichiometry, and hydrogen bonding and van der Waals forces were indicated as the primary drivers. Synchronous fluorescence revealed flavonoid binding disrupted the tryptophan microenvironment but left tyrosine relatively stable. IGM analysis of rutin glycosylation revealed a rigid intramolecular hydrogen-bond network, whereas the aglycones were less stable. Intermolecularly, rutin formed multiple hydrogen bonds and extensive hydrophobic interactions, while aglycone binding was simpler. MD simulations and free energy calculations yielded the following binding affinity: hesperetin > naringenin > rutin, underscoring the importance of solvation effects. This work provides molecular-level insights into the structure-activity relationship, aiding the design of flavonoid delivery systems.
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高影响因子
Food Chemistry-X
·
2023
·
IF 6.1
Chengyun He,Lu Bai,Daqun Liu,Benguo Liu
The binding capacity of 10 flavonoids with okra seed protein (OSP) was studied by fluorescence spectroscopy. The structure of flavonoids had an obvious impact on binding performance. The binding ability of flavanone was lower than that of flavone, isoflavone and dihydrochalcone. The binding capacity of flavonoid glycoside was superior to that of the corresponding flavonoid aglycone. The binding ability was positively correlated with the number of phenolic hydroxyl groups on the B ring. The steric field and electrostatic field model constructed by 3D-QSAR method could well explain the above interaction behavior. Thermodynamic analysis suggested that the quenching mechanism of OSP caused by flavonoids was static quenching, and the binding-site number was 1. In addition, hydrogen bonding and van der Waals force dominated this interaction. The 3D and synchronous fluorescence spectra showed that there was no significant change in the polarity of the environment around tryptophan and tyrosine residues during binding.
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RSC Advances
·
2023
·Vol. 13
·期 16
·10523-10541
·
IF 3.9
Delong Wang,Min Li,Jing Li,Yali Fang,Zhijia Zhang
In an effort to exploit the bioactive natural scaffold 3,4-dihydroisoquinolin-1(2H)-one for plant disease management, 59 derivatives of this scaffold were synthesized using the Castagnoli–Cushman reaction. The results of bioassay indicated that their antioomycete activity against Pythium recalcitrans was superior to the antifungal activity against the other 6 phytopathogens. Compound I23 showed the highest in vitro potency against P. recalcitrans with an EC50 value of 14 μM, which was higher than that of the commercial hymexazol (37.7 μM). Moreover, I23 exhibited in vivo preventive efficacy of 75.4% at the dose of 2.0 mg/pot, which did not show significant differences compared with those of hymexazol treatments (63.9%). When the dose was 5.0 mg per pot, I23 achieved a preventive efficacy of 96.5%. The results of the physiological and biochemical analysis, the ultrastructural observation and lipidomics analysis suggested that the mode of action of I23 might be the disruption of the biological membrane systems of P. recalcitrans. In addition, the established CoMFA and CoMSIA models with reasonable statistics in the three-dimensional quantitative structure–activity relationship (3D-QSAR) study revealed the necessity of the C4-carboxyl group and other structural requirements for activity. Overall, the above results would help us to better understand the mode of action and the SAR of these derivatives, and provide crucial information for further design and development of more potent 3,4-dihydroisoquinolin-1(2H)-one derivatives as antioomycete agents against P. recalcitrans.
研究领域:
植物病理学
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药物化学
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分子生物学
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PubMed
高影响因子
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