PEST MANAGEMENT SCIENCE
·
2016
·Vol. 73
·期 5
·917-924
·
IF 2.811
Qi Liu,Rui Zhu,Shang Gao,Shi-Han Ma,Hai-Jun Tang,Jian-Jun Yang,Ya-Mei Diao,Hong-Lei Wang,Hong-Jun Zhu
BACKGROUND Anthranilic diamide derivatives are among the most important classes of synthetic insecticides. Moreover, the 1,2,4-oxadiazole heterocycle, a bioisostere of amide, has been extensively used in pesticides. In order to discover novel molecules with high insecticidal activities, a series of anthranilic diamide analogues containing 1,2,4-oxadiazole rings were designed and synthesised. RESULTS A series of novel anthranilic diamide derivatives containing 1,2,4-oxadiazole were obtained, and confirmed by 1 H and 13 C nuclear magnetic resonance and high-resolution mass spectrometry. The structure of 3-bromo- N -(4-chloro-2-methyl-6-{3-[(methylsulphonyl)methyl]-1,2,4-oxadiazol-5-yl}phenyl)-1-(3-chloropyridin-2-yl)-1 H -pyrazole-5-carboxamide was further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed 100% mortality against Plutella xylostella at 100 mg L −1 , and compound 3IIl showed 90% larvicidal activities at a concentration of 0.5 mg L −1 . The LC 50 value of 3IIl was 0.20 mg L −1 , which indicated that it may be used as a potential leading compound for further structural optimisation. Furthermore, brief comparative molecular field analysis (CoMFA) models were established to study the structure–activity relationships (SARs) of the title compounds. CONCLUSION Compound 3IIl may be used as a potential leading compound for further structural optimisation, and SARs and CoMFA models could provide reliable clues for further structural optimisation. © 2016 Society of Chemical Industry
研究领域:
农药化学
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有机合成
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生物活性研究
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2013
·
IF 2.906
Bao-Lei Wang,Hong-Wei Zhu,Yi Ma,Li-Xia Xiong,Yong-Qiang Li,Yu Zhao,Ji-Feng Zhang,You-Wei Chen,Sha Zhou,Zheng-Ming Li
Anthranilic diamides are one of the most important classes of modern agricultural insecticides. To discover new structure-modified compounds with high activity, series of novel carbonyl thioureas, carbonyl ureas, oxadiazoles, carbonyl thiophosphorylureas, oxadiazole-containing amides, and thiazoline-containing amides were designed through the modification of the amide bridge based on the structure of chlorantraniliprole and were synthesized, and bioassays were carried out. The compounds were characterized and confirmed by melting point, IR, 1H NMR, and elemental analyses or HRMS. Preliminary bioassays indicated that some compounds exhibited significant insecticidal activities against oriental armyworm, diamondback moth, beet armyworm, corn borer, and mosquito. Among them, trifluoroethoxyl-containing carbonyl thiourea 20a showed best larvicidal activity against oriental armyworm, with LC50 and LC95 values of 0.1812 and 0.7767 mg/L, respectively. Meanwhile, 20c and 20e showed 86 and 57% death rates against diamondback moth at 0.005 mg/L, and the LC50 values of the two compounds were 0.0017 and 0.0023 mg/L, respectively, which were lower than that of the control chlorantraniliprole. The relationship between structure and insecticidal activity was discussed, and the HF calculation results indicated that the carbonyl thiourea moiety plays an important role in the insecticidal activity. The present work demonstrated that the trifluoroethoxyl-containing carbonyl thioureas can be used as lead compounds for further development of novel insecticides.
研究领域:
农业化学
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昆虫学
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有机合成化学
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产品关联
DOI
PubMed
高影响因子
CURRENT ORGANIC SYNTHESIS
·
2023
·Vol. 20
·期 8
·821-837
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IF 1.8
Bhandari Shashikant V.,Kuthe Pranali,Patil Shital Manoj,Nagras Om,Sarkate Aniket Pardip
Introduction: Cancer is the major cause of death globally. Cancer can be treated with naturally occurring Curcumin nuclei. Curcumin has a wide range of biological actions, including anti-inflammatory and anti-cancer properties. Even though it is an effective medicinal entity, it has
some limitations such as instability at physiological pH and a weak pharmacokinetic profile due to the β-diketone moiety present in it. To overcome this drawback, research was carried out on monoketone moieties in curcumin, popularly known as mono-carbonyl curcumin. Objective: The
present review focuses on different synthetic schemes and Mono-carbonyl curcumin derivative's Structure-Activity Relationship (SAR) as a cytotoxic inhibitory anticancer agent. The various synthetic schemes published by researchers were compiled. Methods: Findings of different researchers
working on mono-carbonyl curcumin as an anticancer have been reviewed, analyzed and the outcomes were summarized. Results: The combination of all of these approaches serves as a one-stop solution for mono-carbonyl curcumin synthesis. The important groups on different positions of mono-carbonyl
curcumin were discovered by a SAR study focused on cytotoxicity, which could be useful in the designing of its derivatives. Conclusion: Based on our examination of the literature, we believe that this review will help researchers design and develop powerful mono-carbonyl curcumin derivatives
that can be proven essential for anticancer activity.
研究领域:
药理学
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肿瘤学
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有机化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Pan-Long Chu,Yu-Mei Feng,Zhou-Qing Long,Wan-Lin Xiao,Jin Ji,Xiang Zhou,Pu-Ying Qi,Tai-Hong Zhang,Heng Zhang,Li-Wei Liu,Song Yang
As quorum sensing (QS) regulates bacterial pathogenicity, antiquorum sensing agents have powerful application potential for controlling bacterial infections and overcoming pesticide/drug resistance. Identifying anti-QS agents thus represents a promising approach in agrochemical development. In this study, the anti-QS potency of 53 newly prepared benzothiazole derivatives containing an isopropanolamine moiety was analyzed, and structure–activity relationships were examined. Compound D3 exhibited the strongest antibacterial activity, with an in vitro EC50 of 1.54 μg mL–1 against Xanthomonas oryzae pv oryzae (Xoo). Compound D3 suppressed QS-regulated virulence factors (e.g., biofilm, extracellular polysaccharides, extracellular enzymes, and flagella) to inhibit bacterial infection. In vivo anti-Xoo assays indicated good control efficiency (curative activity, 47.8%; protective activity, 48.7%) at 200 μg mL–1. Greater control efficiency was achieved with addition of 0.1% organic silicone or orange peel essential oil. The remarkable anti-QS potency of these benzothiazole derivatives could facilitate further novel bactericidal compound development.
研究领域:
农业科学
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微生物学
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有机化学
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DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 98
·55445-55451
·
IF 3.708
Qi Liu,Kai Chen,Qiang Wang,Jueping Ni,Yufeng Li,Hongjun Zhu,Yuan Ding
A series of anthranilic diamides analogs (5a–x) containing 1,3,4-oxadiazole rings were synthesized and characterized by 1H NMR, 13C NMR and mass spectrometry. The structure of N-(4-chloro-2-methyl-6-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl)phenyl)methacrylamide (5u) was determined by X-ray diffraction crystallography. The insecticidal activities of these new compounds against diamondback moth (Plutella xylostella) were evaluated. Preliminary bioassays indicated that some of these compounds exhibited good insecticidal activities against P. xylostella, especially 3-bromo-N-(4-bromo-2-methyl-6-(5-(pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (5d), which displayed 100%, 80.95% and 57.14% activity against P. xylostella at 40 μg mL−1, 10 μg mL−1 and 4 μg mL−1, respectively. The relationship between structure and insecticidal activity was discussed. The density functional theory (DFT) studies could be helpful to understand the various insecticidal activities.
研究领域:
农药化学
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有机化学
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昆虫学
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DOI
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2022
·Vol. 38
·期 4
·949-956
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IF 2.726
Ruan Yawen,Huang Peiling,Yan Jiangyu,Li Guorui,Huang Jing
Targeted prodrug strategy, which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug, has been well established either in the fundamental research or the clinical treatment. However, many prodrugs suffer from safety concern due to “off-target activation”. Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the “off-target effect”. Melanoma cells have both high levels of reactive oxygen species(ROS) and tyrosinase(TYR), which makes them significantly different from other tumor cells and normal cells. Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs, which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells. The structure-activity relationship(SAR) analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells. Among these candidates, compound 4 b showed the highest toxicity to B16, leading to an imbalance of the redox system in melanoma cells, causing mitochondrial DNA damage, and then promoting melanoma cells death.
研究领域:
肿瘤学
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药物化学
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分子生物学
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药理学
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DOI
高影响因子
MEDICINAL CHEMISTRY RESEARCH
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2022
·Vol. 32
·期 2
·288-313
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IF 2.351
Zhang Yuanwen,Zheng Yueming,Wu Qingqing,Tian Fuyun,Ma Chuanjun,Xu Haiyan,Zhan Li,Gao Zhaobing,Zhao Guilong,Ti Huihui
A clinical therapy for chronic neuropathic pain is urgently needed, and the voltage-gated calcium channel (VGCC) α2δ subunit is among the most promising therapeutic targets. To intensively explore the structure-activity relationship (SAR) of the lipophilic moiety in VGCC α2δ subunit ligands (gabapentinoids), we designed and synthesized 11 bicyclic and monocyclic derivatives based on mirogabalin, a third-generation VGCC α2δ subunit ligand. The competitive binding of the synthesized compounds to the human VGCC α2δ-1 subunit was measured in vitro, and the results demonstrated that the lipophilic moiety size was strictly limited in gabapentinoids, in which conformationally rigid bicylo[3.2.0]heptane/heptene with a cis -fusion was the most preferred structure. In contrast, monocyclic cyclobutane was associated with a markedly decreased binding affinity except in 4 (IC 50 = 15.2 nM), in which the substituents could mimic the rigid conformation of bicylo[3.2.0]heptane/heptene; heteroatoms in the lipophilic moiety were detrimental to the binding affinity ( 2 , IC 50 > 729 nM). The SAR findings obtained in the present study will be valuable for designing novel gabapentinoid drugs to treat chronic neuropathic pain in the future. Graphical abstract
研究领域:
药理学
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神经科学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Li-Yuan Wei,Yu-Wei Lin,Jia-Chun Luo,Yi-Xian Li,Yu-Tao Hu,Shi-Yao Guo,Zhi Jiang,Dan-Dan Zhao,Shuo-Bin Chen,Zhi-Shu Huang
ABSTRACT Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga , which significantly reduced TG accumulation with an EC 50 value of 0.07 μM and showed relatively low cytotoxicity with an IC 50 value of around 24 μM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d . A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity.
研究领域:
药理学
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药物化学
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Menglong Zhao,Danqing Wu,Weiqian Qiu,Hongchen Zhang,Min Chen,Haixia Zhou,Xiaoxia Ye,Zhong Han,Xiangchao Shi
4-anilinoquinazoline scaffold, a key structure in the development of EGFR-TKI anticancer drugs such as Gefitinib and Erlotinib, continues to drive advancements in non-small cell lung cancer (NSCLC) therapy. In this study, we synthesized a series of novel derivatives ( B3–B11 ). Structure-activity relationship (SAR) analysis revealed that electron-donating groups para-substituted at the 4-anilino position significantly enhanced antiproliferative activity. Notably, B10 incorporating an acrylamide group at the 4-anilino position demonstrated the most potent activity against NSCLC, with an IC 50 of 1.28 μM in A549 cells, nearly six times more effective than Gefitinib (7.81 μM). Acute toxicity studies confirmed that B10 is safe at doses below 50 mg/kg. In vivo studies using an A549 xenograft model showed a 46 % tumor growth inhibition (TGI) with B10 (25 mg/kg), surpassing the 21 % inhibition of Gefitinib at the same dose. Mechanistic studies revealed that B10 inhibited the AKT/GSK-3β/β-catenin signaling pathway, downregulating Wnt target genes (c-Myc, c-Jun), and reduced COX2 expression and IL-8 levels, showcasing its dual anti-inflammatory and antitumor effects. These results position B10 as a promising NSCLC therapeutic candidate, combining potent efficacy with a favorable safety profile, and enhance our understanding of the SAR and mechanism of action of 4-anilinoquinazoline derivatives.
研究领域:
肿瘤学
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药理学
·
分子生物学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 11
·2275-2285
·
IF 5.344
Ya-Ping Xiao,Ji Zhang,Yan-Hong Liu,Zheng Huang,Yu Guo,Xiao-Qi Yu
Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure–activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of β-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.
研究领域:
生物材料
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基因治疗
·
蛋白质工程
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纳米技术
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药剂学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Hao-Min Song,Li-Xia Zhao,Shuai-Qi Zhang,Tong Ye,Ying Fu,Fei Ye
Cinnamic acid, isolated from cinnamon bark, is a natural product with excellent bioactivity, and it effectively binds with cyclohexanedione to form novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. According to the active sub-structure combination principle, a series of novel 3-hydroxy-2-cinnamoyl-2-en-1-one derivatives were designed and synthesized. The title compounds were characterized by infrared, 1H NMR, 13C NMR, and HRMS. The in vitro inhibitory activity of AtHPPD verified that compound II-13 showed the most activity with a half-maximal inhibitory concentration (IC50) value of 0.180 μM, which was superior to that of mesotrione (0.206 μM) in vitro. The preliminary herbicidal activity tests demonstrated that some compounds had good herbicidal activity especially compound II-13 at a concentration of 150 g ai/ha. The binding mode of AtHPPD through molecular docking indicated that two oxygens of compounds II-13 formed bidentate interactions with metal ions, and the benzene ring formed π-π accumulation effects with Phe-381 and Phe-424. The results of molecular dynamics simulations showed that compound II-13 exhibited a more stable binding ability with AtHPPD than mesotrione. This study provided insights into the development of natural and efficient herbicides in the future.
研究领域:
化学
·
药理学
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农业科学
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分子生物学
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植物科学
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DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2024
·
IF 5.6
Xin Gan,Yuna Wu,Min Zhu,Bo Liu,Miaomiao Kong,Zixuan Xi,Ke Li,Haibao Wang,Tiande Su,Jiali Yao,Fatehi Khushafah,Baozhu Yi,Jiabing Wang,Wulan Li,Jianzhang Wu
The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.
研究领域:
肿瘤学
·
药物化学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）