AUSTRALIAN JOURNAL OF CHEMISTRY
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2018
·Vol. 71
·期 6
·449-454
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IF 1.059
Fu-Rong Zeng,Qi-Lin Zhu,Zi-Long Li
Post-polymerization modification is a facile and efficient method for the generation of diverse functional polymers. Herein, polymer-based molecular arrays were obtained by using sequential modification. First, periodic polyketone P0 was synthesized via acyclic diene metathesis (ADMET) polymerization of α,ω-diene M0. Oxime chemistry was employed in the functionalization of the ketone moieties of P0 using three commercially available alkoxyamine hydrochlorides. Finally, electrophilic alkoxyetherification, a four-component reaction, was employed in the modification of alkene groups on polymer main chains using N-bromosuccinimide (NBS), tetrahydrofuran, and fluorinated carboxylic acid. Complete conversion of reactive sites was observed in both steps, and the two modification reactions exhibited excellent compatibility. The thermal properties of the polymers as thermal stability, and glass transition and melting behaviours were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC).
研究领域:
材料科学
·
有机化学
✓ 已验证
DOI
高影响因子
MACROMOLECULES
·
2020
·
IF 5.918
Xiaoqing Liu,Taixin Chen,Feng Yu,Yuxuan Shang,Xue Meng,Zhong-Ren Chen
Using acyclic diene metathesis (ADMET) polymerization, we have synthesized a series of random conjugated copolymers from diene monomers based on tetraphenylethene (TPE), which is an aggregation-induced emission (AIE)-active molecule, and comonomers such as 1,9-decadiene, 2,7-divinyl-9,9-di-n-octylfluorene, and 1,4-dihexyl-2,5-divinylbenzene. These all-hydrocarbon copolymers exhibit good solubility and high molecular weights. As proved by 1H NMR spectra, chain segments composed of two monomers are randomly distributed in the polymers. Absorption and emission features from both TPE units and those conventional diene segments in conjugated copolymers are observed in their optical spectra. Because of the presence of AIE-active TPE units, emission intensities of the copolymers are greatly enhanced in tetrahydrofuran/water mixtures with increased water content. Moreover, the fluorescence of ADMET polymers can be quenched by palladium ions in quasi-aqueous solutions following a dynamic quenching mechanism. The fluorescence quench degrees are affected by both chemical structures of the copolymers and the solvent polarity. Our findings demonstrate that ADMET conjugated polymers have enormous potential as fluorescent “turn-off” probes specific for palladium ions even in the absence of a particular coordination interaction.
研究领域:
化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2022
·
IF 4.966
Ling Jia,Li-Xia Zhao,Fang Sun,Jie Peng,Jia-Yu Wang,Xin-Yu Leng,Shuang Gao,Ying Fu,Fei Ye
Flumioxazin, a protoporphyrinogen oxidase (PPO; EC 1.3.3.4) inhibitor, has been used in soybean, cotton, grapes, and many other crops to control broad leaf weeds. Unfortunately, it can cause damage to cotton. To ameliorate phytotoxicity of flumioxazin to cotton, this work assessed the protective effects of diazabicyclo derivatives as potential safeners in cotton. A bioactivity assay proved that the phytotoxicity of flumioxazin on cotton was alleviated by some of the compounds. In particular, the activity of glutathione S-transferases (GSTs) was significantly enhanced by Compound 32 , which showed good safening activity against flumioxazin injury. The physicochemical properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions proved that the pharmacokinetic properties of Compound 32 are similar to those of the commercial safener BAS 145138. The present work demonstrated that diazabicyclo derivatives are potentially efficacious as herbicide safeners, meriting further investigation.
研究领域:
农业科学
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植物生理学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STRUCTURE
·
2023
·
IF 5.7
Jin Dong,Han Xiao,Jia-Nan Chen,Bai-Feng Zheng,Yu-Ling Xu,Meng-Xi Chen,Wen-Chao Yang,Hong-Yan Lin,Guang-Fu Yang
4-Hydroxyphenylpyruvate dioxygenase (HPPD) has attracted increasing attention as a target for treating type I tyrosinemia and other diseases with defects in tyrosine catabolism. Only one commercial drug, 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), clinically treat type I tyrosinemia, but show some severe side effects in clinical application. Here, we determined the structure of human HPPD-NTBC complex, and developed new pyrazole-benzothiadiazole 2,2-dioxide hybrids from the binding of NTBC. These compounds showed improved inhibition against human HPPD, among which compound a10 was the most active candidate. The Absorption Distribution Metabolism Excretion Toxicity (ADMET) predicted properties suggested that a10 had good druggability, and was with lower toxicity than NTBC. The structure comparison between inhibitor-bound and ligand-free form human HPPD showed a large conformational change of the C-terminal helix. Furthermore, the loop 1 and α7 helix were found adopting different conformations to assist the gating of the cavity, which explains the gating mechanism of human HPPD.
研究领域:
药理学
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药物化学
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Xu Xuemei,Zhu Zhaojingtao,Chen Siyu,Fu Yanneng,Zhang Jinxia,Guo Yangyang,Xu Zhouyang,Xi Yingying,Wang Xuebao,Ye Faqing,Chen Huijun,Yang Xiaojiao
Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study’s mechanistic exploration, highlighting B7’s simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.
研究领域:
药理学
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肿瘤学
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药物化学
·
细胞生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Li Guan,Shengjie Zhang,Pengfei Song,Yanxin Xia,Xinle Zheng,Weize Li
The inhibition of angiogenesis has been considered as an attractive method for the discovery of potential anti-cancer drugs. Herein, we report our new synthesized bibenzyl compound Ae had potent anti-angiogenic activity(the lowest effective concentration is to 0.62–1.25 μM) in zebrafish in vivo and showed a concentration-dependent inhibition of inter-segmental blood vessels (ISVs) compared to control. Further, Ae exhibited the obvious inhibitory activity of proliferation, migration, invasion and tube formation in HUVEC cells in vitro . Moreover, qRT-PCR analysis revealed that the anti-angiogenic activity of compound Ae is connected with the ang-2 , tek in ANGPT-TEK pathway and the kdr, kdrl signaling axle in VEGF-VEGFR pathway. Molecular docking studies revealed that compound Ae had an interaction with the angiopoietin-2 receptor(TEK) and VEGFR2. Additionally, analysis of the ADMET prediction data indicated that compound Ae possessed favorable physicochemical properties, drug-likeness, and synthetic accessibility. In conclusion, compound Ae had remarkable anti-angiogenic activity and could be served as an candidate for cancer therapy.
研究领域:
药理学
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肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Zhan Cui,Fang-Yan Guo,Li Li,Fuping Lu,Cheng-Hua Jin,Xiangming Wang,Fufeng Liu
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the accumulation of α-synuclein (α-Syn) aggregates. However, there are currently no effective therapies for PD. Brazilin, an inhibitor of α-Syn aggregation, is unstable and toxic. Therefore, we have developed and synthesized derivatives of brazilin. One of these derivatives, called brazilin-7-acetate (B-7-A), has shown reduced toxicity and a stronger effect on inhibit α-Syn aggregation. It showed that B-7-A prevented the formation of α-Syn fibers and disrupted existing fibers in a dosage-dependent manner. Additionally, B-7-A significantly reduced the cytotoxicity of α-Syn aggregates and alleviated oxidative stress in PC12 cells. The beneficial effects of B-7-A were also confirmed using the Caenorhabditis elegans model. These effects included preventing the accumulation of α-Syn clumps, improving behavior disorder, increasing lifespan, reducing oxidative stress, and protecting against lipid oxidation and loss. Finally, B-7-A showed good ADMET properties in silico. Based on these findings, B-7-A exhibits potential as a prospective treatment for PD.
研究领域:
神经学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Jinfu Wang,Yan Guo,Huifen Zhou,Yanjie Hua,Haitong Wan,Jiehong Yang
Objective: Cardiac ischemia-reperfusion (I/R) injury has negative effects on the brain and can even lead to the occurrence of ischemic stroke. Clinical evidence shows that Danhong injection (DHI) protects the heart and brain following ischemic events. This study investigated the mechanisms and key active compounds underlying the therapeutic effect of DHI against brain damage induced by cardiac I/R injury. Methods: The gene expression omnibus database provided GSE66360 and GSE22255 data sets. The R programming language was used to identify the common differentially expressed genes (cDEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed, and protein–protein interaction network was constructed. Active compounds of DHI were collected from the Traditional Chinese Medicine Systems Pharmacology database. Molecular docking and molecular dynamics simulations were performed. The MMPBSA method was used to calculate the binding-free energy. The pkCSM server and DruLiTo software were used for Absorption, Distribution, metabolism, excretion, and toxicity (ADMET) analysis and drug-likeness analysis. Finally, in vitro experiments were conducted to validate the results. Results: A total of 27 cDEGs had been identified. The PPI and enrichment results indicated that TNF-α was considered to be the core target. A total of 80 active compounds were retrieved. The molecular docking results indicated that tanshinone I (TSI), tanshinone IIA (TSIIA), and hydroxyl safflower yellow A (HSYA) were selected as core active compounds. Molecular dynamics verification revealed that the conformations were relatively stable without significant fluctuations. MMPBSA analysis revealed that the binding energies of TSI, TSIIA, and HSYA with TNF-α were −36.01, −21.71, and −14.80 kcal/mol, respectively. LEU57 residue of TNF-α has the highest contribution. TSI and TSIIA passed both the ADMET analysis and drug-likeness screening, whereas HSYA did not. Experimental verification confirmed that DHI and TSIIA reduced the expression of TNF-α, NLRP3, and IL-1β in the injured H9C2 and rat brain microvascular endothelial cells. Conclusion: TNF-α can be considered to be a key target for BD-CI/R. TSIIA in DHI exerts a significant inhibitory effect on the inflammatory damage of BD-CI/R, providing new insights for future drug development.
研究领域:
药理学
·
生物信息学
·
神经科学
·
心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2022
·
IF 3.841
Aihong Yang,Wenjing Liu,Xiangyu Li,Wanru Wu,Xiaodi Kou,Rui Shen
More and more evidence suggested that bio-metals including iron, zinc and copper play an important role in Alzheimer's disease (AD). Metal chelation agents may play an important role through promoting the metal homeostasis for AD treatment. In this study, UA (usnic acid), a natural product with antioxidant activity and metal chelation sites was selected as a lead compound. Different types of tertiary amine groups were introduced to synthesize four UA derivatives 1–4 as metal chelators and cholinesterase inhibitors since tertiary amine moiety was the key pharmacophore to inhibit cholinesterase. And the related activities such as antioxidant, anti-cholinesterase and metal chelation were evaluated. Results showed that 1–4 displayed excellent anti-oxidant activity, with lowest IC 50 of 0.433 µM for ·OH scavenging ability and 8.808 µM for ·O 2 − scavenging ability. The mechanisms of anti-oxidant activities were furtherly studied by cyclic voltammetry. Besides, 1–4 also showed good anti-cholinesterase activities with lowest IC 50 of 0.269 µM for acetylcholinesterase (AChE) and 0.361 µM for butyrylcholinesterase (BuChE). The results of molecular docking with AChE and BuChE were consistent with the experimental results. 1–4 displayed obvious chelating abilities with Cu(II) and Fe(III) by UV–vis spectra analysis and the metal complexes also showed good anti-AD activities. Interestingly, single crystal of Cu(II) complex of the hydrolyzed mono-substituted ligand was obtained which further substantiated the metal binding ability and provided clues to the anti-AD activities of the metal complex. Meanwhile, hydrolysis ratio of 4 was also tested by HPLC. Finally, BBB permeability of 1–4 was acceptable by ADMET prediction. Overall, these findings demonstrated that compounds 1–4 might be considered as potential candidates in the anti-AD therapy.
研究领域:
药理学
·
药物化学
·
神经科学
·
无机化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）