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
·
毒理学
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PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 2
·607
·
IF 4.6
Juntao Guo,Yihui Zhang,Jinjun Li,Feng Wu,Liting Luo
Pyrite has been used in photo-Fenton reactions for the degradation of pollutants, but the application of photo-Fenton processes with extra H2O2in real water/wastewater treatment has still been limited by the economic cost of H2O2and artificial light sources. Herein, citric acid (CA) and simulated/natural sunlight are used to develop a pyrite-based photo-Fenton system (pyrite–CA–light) in situ generating H2O2through the enhanced activation of molecular oxygen. The degradation of pharmaceuticals and personal care products (PPCPs), especially acetaminophen (APAP) as the main target pollutant, in the pyrite–CA–light system was investigated. The effects of influencing factors such as various organic acids, APAP concentration, pH, pyrite dosage, CA concentration and co-existing anions (HCO3−, Cl−, NO3−, SO42−and H2PO4−) were examined. At a pyrite dosage of 0.1 g L−1, CA concentration of 0.6 mM and an initial pH of 6.0, the degradation efficiency of APAP (30 μM) was 99.1% within 30 min under the irradiation of xenon lamp (70 W, λ ≥ 350 nm). Almost the same high efficiency of APAP degradation (93.9%) in the system was achieved under natural sunlight irradiation (ca. 650 W m−2). The scavenging experiments revealed that the dominant active species for degrading APAP was hydroxyl radical (HO•). Moreover, a quantitative structural–activity relationship (QSAR) model for pseudo-first-order rate constants (kobs) was established with a high significance (R2= 0.932,p= 0.001) by using three descriptors: octanol–water partition coefficient (logKow), dissociation constant (pKa) and highest occupied molecular orbital (HOMO). This work provides an innovative strategy of the photo-Fenton process for the degradation of PPCPs using natural minerals and ordinary carboxylic acid under sunlight.Keywords:pyrite;citric acid;sunlight;photo-Fenton;PPCPs;QSAR
研究领域:
环境科学
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化学工程
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PubMed
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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DOI
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Jia-Yi Yin,Ya-Ning Han,Meng-Qi Liu,Zan-Hao Piao,Xu Zhang,Yu-Ting Xue,Ying-Hua Zhang
Human health can be damaged by free radicals, and antioxidant peptides are excellent radical scavengers. Antioxidant tripeptides data set based on 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulofnic acid) (ABTS) assay was created, 9 types of descriptors were integrated and 4 quantitative structure–activity relationship (QSAR) models were constructed in this study. Several structural factors influencing the activity of antioxidant tripeptides and the dominant amino acids at each position of tripeptides were revealed by the optimal model. Ten food-derived tripeptides with higher activity were selected for synthesis and activity determination. Molecular docking results demonstrated that these tripeptides were stably bound to the Keap1 receptor, further elucidating the antioxidant mechanism. It was known from the simulation of gastrointestinal digestion experiments that the model results possessed a guiding effect on the selection of proteins with high antioxidant activity . The performance of the model was proved to be robust after validation.
研究领域:
生物信息学
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营养学
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分子生物学
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Guanting Li,Meixiu Lu,Zixuan Jiao,Shunzhe Zheng,Hongying Xiao,Meng Li,Jianbin Shi,Xinying Liu,Zhonggui He,Bingjun Sun,Jin Sun
Small-molecule prodrug nanoassemblies (SMP-NAs) represent a promising nanomedicine for cancer therapy, enabling carrier-free characteristics and facile fabrication. However, the development of SMP-NAs currently relies on empirical trial-and-error screening, as quantitative descriptors to predict the relationship between molecular structure and self-assembly remain unavailable. Here, we introduce chemical topology indices, traditionally restricted to small-molecule drug discovery, as predictive tools for the rational design of SMP-NAs. We synthesized three topological SN38 prodrugs with distinct topological architectures (linear, cyclic and branched) but identical lipophilicity. Topological indices quantitatively capture the critical molecular characteristics of the prodrugs. Notably, the branched architecture (SN38-Br) provides molecular flexibility for efficient core packing while maintaining sufficient steric hindrance to prevent over-aggregation. Consequently, SN38-Br NPs exhibited superior colloidal stability, systemic blood circulation, robust tumor accumulation and antitumor activity. Our work establishes a theoretical framework for the quantitative structure-activity relationship (QSAR) of SMP-NAs, offering a blueprint for the transition from empirical screening to Nano-QSAR.
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高影响因子
Journal of Fungi
·
2022
·Vol. 8
·期 8
·762
·
IF 5.724
Xinying Duan,Li Zhang,Hongyan Si,Jie Song,Peng Wang,Shangxing Chen,Hai Luo,Xiaoping Rao,Zongde Wang,Shengliang Liao
Control of fungal phytopathogens affecting crops and woodlands is an important goal in environmental management and the maintenance of food security. This work describes the synthesis of 37 camphor derivatives, of which 27 were new compounds. Their antifungal effects on six fungi were evaluated in vitro. Compounds3a,4aand5kshowed strong antifungal activity againstTrametes versicolor, with EC50values of 0.43, 6.80 and 4.86 mg/L, respectively, which were better than that of tricyclazole (EC50118.20 mg/L) and close to or better than that of carbendazim (EC501.20 mg/L). The most potent compound,3a, exhibited broad-spectrum antifungal activity towards six fungi with EC50values within the range of 0.43–40.18 mg/L. Scanning electron microscopy demonstrated that compounds3a,4aand5kgave irregular growth and shriveling of the mycelia. In vitro cytotoxicity evaluation revealed that the tested camphor derivatives had mild or no cytotoxicity for LO2and HEK293T cell lines. Quantitative structure−activity relationship (QSAR) analysis revealed that the number of F atoms, relative molecular weight, the atomic orbital electronic population and total charge on the positively charged surfaces of the molecules of camphor derivatives have effects on antifungal activity. The present study may provide a theoretical basis for a high-value use of camphor and could be helpful for the development of novel potential antifungals.Keywords:camphor;synthesis;antifungal activity;cytotoxicity;QSAR
研究领域:
植物保护
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药物化学
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环境科学
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PubMed
高影响因子
MOLECULES
·
2014
·Vol. 19
·期 6
·7287-7307
·
IF 2.095
Yali Zhang,Leping Zhao,Jianzhang Wu,Xin Jiang,Lili Dong,Fengli Xu,Peng Zou,Yuanrong Dai,Xiaoou Shan,Shulin Yang,Guang Liang
Curcumin has been reported to possess multiple bioactivities, such as antioxidant, anticancer, and anti-inflammatory properties, however the clinical application of curcumin has been significantly limited by its instability and poor metabolism. Modification of curcumin has led to discovery and development of lots of novel therapeutic candidates. In recent years acute and chronic inflammation has been the focus of numerous studies in various diseases. Here, we synthesized a series of asymmetrical curcumin analogs with highin vitrochemical stability, and their anti-inflammatory activity was evaluated in LPS-stimulated macrophages. According to the bio-screening results and QSAR analysis, these analogs exhibited potent activities against LPS-induced TNF-α and IL-6 release. Among the analogs of the potent anti-inflammatory activity, compounds3b8and3b9exhibited significant protection and possess enhanced anti-inflammatory activity thereby attenuated the LPS-induced septic death in mice.Keywords:curcumin;asymmetrical curcumin analogs;anti-inflammation;QSAR;cytokines
研究领域:
药理学
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免疫学
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PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 30
·21432-21438
·
IF 3.9
Yunkai Sun,Xiaoxia Wu,Pei Zuo,Zhao Liu,Xuepei Miao,Jian Liu,Hairuo Wen
In the technical route for the synthesis of avanafil, 1-ethyl-(3-dimethylaminopropyl)carbamyldiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBT) are used as reactive acid–amine binding agents. HOBT contains trace amounts of hydrazine residue, and there is a risk of introducing potentially mutagenic impurities with hydrazide-containing structures. The potentially genotoxic impurities E (Imp-E) and F (Imp-F) of avanafil with altering hydrazide-structure were synthesized by chemical method; subsequently, the impurities were evaluated and classified according to ICH M7 guidelines. Two complementary quantitative structure–activity relationship (QSAR) evaluation systems (Derek and Sarah) based on expert rules and statistics were used to preliminarily predict the genotoxicity of Imp-E and Imp-F, and the prediction result of E was suspected to be positive. In the Ames test of Imp-E and Imp-F, in the dose range of 62.5–1000 μg per plate, with or without the presence of metabolic activation system S9, the number of revertant colonies did not exceed 2 times the number of colonies in the solvent control group and did not show a dose–response relationship, and the test results were negative. Imp-E and Imp-F were determined to be negative for genotoxicity, which could be controlled as class 5 in ICH M7, that is, non mutagenic impurity.
研究领域:
药物化学
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毒理学
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制药工程
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 8
·e71542
·
IF 2.9
Min Xiao,Haowen Huang,Dagen Wang,Lili Yao,Shengliang Liao,Jie Song,Rong Zeng,Shangxing Chen
To develop citral‐based botanical fungicides, 112 previously reported derivatives across 5 series were evaluated in vitro against Colletotrichum fructicola . SAR analysis identified the citral‐thiourea series as the most potent group, with 3‐methoxy derivative c18 showing the highest intraseries activity. Notably, intermediates d (EC 50 = 0.7474 mg/L, EC 90 = 6.0319 mg/L) and g (EC 50 = 0.1073 mg/L, EC 90 = 0.6244 mg/L) demonstrated exceptional efficacy, significantly outperforming commercial chlorothalonil (EC 50 = 1.4382 mg/L, EC 90 = 268.5969 mg/L), with intermediate g emerging as the most potent compound overall. A predictive QSAR model was successfully constructed ( R 2 = 0.8345), revealing that lower polarity, enhanced electronic stability of carbon–hydrogen bonds, higher localized solvation energy, and minimized steric hindrance favor antifungal potency. Furthermore, MTT assays confirmed that derivative g exhibits low cytotoxicity toward human liver and kidney cells, substantially lower than raw citral. This work provides a solid theoretical framework for designing highly active inhibit C. fructicola agents. A library of 112 previously reported citral derivatives is screened to identify potent botanical fungicides against Colletotrichum fructicola . A predictive QSAR model ( R 2 = 0.8345) decrypts structural pathways, elegantly balancing global transmembrane transport with localized target anchoring. Providing exceptional efficacy and low cytotoxicity, these insights offer a definitive blueprint for the next‐generation green pesticides.
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高影响因子
Journal of Chemical Information and Modeling
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2024
·
IF 5.6
Xu Li,Haoliang Zhong,Haoyu Yang,Lin Li,Qingji Wang
Nucleophilic index (NNu) as a significant parameter plays a crucial role in screening of amine catalysts. Indeed, the quantity and variety of amines are extensive. However, only limited amines exhibit an NNu value exceeding 4.0 eV, rendering them potential nucleophiles in chemical reactions. To address this issue, we proposed a computational method to quickly identify amines with high NNu values by using Machine Learning (ML) and high-throughput Density Functional Theory (DFT) calculations. Our approach commenced by training ML models and the exploration of Molecular Fingerprint methods as well as the development of quantitative structure–activity relationship (QSAR) models for the well-known amines based on NNu values derived from DFT calculations. Utilizing explainable Shapley Additive Explanation plots, we were able to determine the five critical substructures that significantly impact the NNu values of amine. The aforementioned conclusion can be applied to produce and cultivate 4920 novel hypothetical amines with high NNu values. The QSAR models were employed to predict the NNu values of 259 well-known and 4920 hypothetical amines, resulting in the identification of five novel hypothetical amines with exceptional NNu values (>4.55 eV). The enhanced NNu values of these novel amines were validated by DFT calculations. One novel hypothetical amine, H1, exhibits an unprecedentedly high NNu value of 5.36 eV, surpassing the maximum value (5.35 eV) observed in well-established amines. Our research strategy efficiently accelerates the discovery of the high nucleophilicity of amines using ML predictions, as well as the DFT calculations.
研究领域:
化学信息学
·
计算化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
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
PLoS One
·
2015
·Vol. 10
·期 3
·e0121276
·
IF 3.234
Yuzhen Chen,Huizhi Xiao,Jie Zheng,Guizhao Liang
Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH • scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH • . Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media.
研究领域:
化学
·
生物学
·
药理学
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PubMed
高影响因子
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