JOURNAL OF HETEROCYCLIC CHEMISTRY
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2015
·Vol. 54
·期 1
·784-788
·
IF 0.787
Fang-Ming Wang,Dan Bao,Bing-Xiang Hu,Ze-Yu Zhou,Deng-Deng Huang,Li-Zhuang Chen,Yuan-Yuan Dan
A series of novel 10-substituted 3,6-diphenyl-9-aryl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione derivatives 2 were synthesized by condensation of compounds 1 with amines, which the compounds 1 were synthesized by 5-phenylcyclohexane-1,3-dione and aromatic aldehydes according to Knoevenagel, Michael, and cyclization reactions in the presence of a very small amount of l-proline as catalyzed at room temperature. The structures of all the synthesized compounds were characterized by IR, 1H NMR, and MS. In addition, the molecular structures of compound 1a have been determined by single-crystal X-ray diffraction analysis.
研究领域:
有机化学
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药物化学
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生物化学
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DOI
高影响因子
Oncotarget
·
2016
·
IF 5.008
Tao Liu,Xidong Wu,Yigang Wang,Tao Zhang,Ting Wu,Fang Liu,Wansong Wang,Gang Jiang,Minqiang Xie
The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.
研究领域:
药剂学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL PHYSICS LETTERS
·
2019
·
IF 1.901
Miaomiao Zhou,Lian Wang,Song Zhang,Bing Zhang
The ultrafast charge transfer (CT) and the following intersystem crossing (ISC) processes of 9-anthraldehyde were investigated in ethanol and hexane using femtosecond transient absorption spectroscopy combined with quantum chemical calculations. The CT was observed within 0.11 ps in ethanol and 0.23 ps in hexane. Due to the stronger polarity in ethanol, the CT is faster than in hexane. The following ISC is determined to be 22.3 ps and 21.4 ps in two solvents, respectively. However, the timescales of ISC are similar in both solvents since the excited energies of the S 1 and triplet states are close.
研究领域:
物理化学
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光化学
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产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Yuan Kong,Yong-Jia Yi,Xiao-Qing Liu,Pan Yu,Lin-Guo Zhao,Dong-Dong Li
Berberine is a quaternary isoquinoline alkaloid that exhibits potent hypoglycemic and hypolipidemic activity. Many medicinal chemists are currently working on structural modifications around the parent scaffold of berberine, expecting to further enhance its hypolipidemic activity and reducing its cytotoxicity. In this study, a focused berberine-like compound library containing 12,600 molecules was built via the introduction of various “drug-like” fragments at the C8 and C9 positions of berberine. Sixteen comopounds were hit by using the in-house QSAR models previously reported by our group. Considering synthesis feasibility and the cost of building-blocks, only four berberine analogs (library ID: 2028 , 3847 , 6033 , and 12456 ) were selected and synthesized for investigating their lipid-lowering activities. Preliminary lipid-lowering study showed that compound 12456 with the phenylsulfonyl group at the C9 position had potent cholesterol inhibitory activity in HepG2 cells, superior to that of the parent compound berberine. Subsequently, a total of twenty-five 9- O -phenylsulfonyl-berberines ( 1a - 1y ) and twenty-four 9- O -phenylsulfonyl-tetrahydroberberine ( 2a - 2x ) were designed, synthesized, and evaluated by lipid-lowering experiments. The results displayed that most compounds exhibited more lipid-lowering activities than berberine. Among them, compound 1m inhibited cholesterol production close to 50% in both cell models when compared with the blank control; the inhibition of triglycerides exceeded 70%. Moreover, 1m also had significant pharmacological effects on the inhibition of LDLC and promotion of HDLC production, especially in the HepG2 cell model, in which the inhibitory rate against LDLC was close to 70% and the increase rate of HDLC was more than 75%. The hypolipidemic experiment of SD rats demonstrated that after 40 days of administration ( 1m , 15 mg/kg/d), blood cholesterol was reduced by 19.6%, triglycerides reduced by 34.52%, and LDLC reduced by 41.49%, when compared with the high-fat diet model (HFD). In addition, after 80 days of administration, the three indexes of 1m were still better than that of berberine. Oil Red O staining and H&E staining results showed that 1m exhibited potent lipid scavenging activity. All in all, 1m was discovered and identified as a potent lipid-lowering agent and a new berberine-like candidate, being evaluated by subsequent studies.
研究领域:
药理学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY
·
2021
·Vol. 36
·期 2
·279-284
·
IF 4.023
Min Jiang,Zili Huang,Xin Zhao,Rui Liu,Yi Lv
Pancreatic cancer is a malignant tumour with high mortality. Surgery after diagnosis at the early stage is the most effective treatment. As the most effective biomarker of pancreatic cancer, CA19-9 has important clinical significance for both early diagnosis and surgical prediction. Herein, a single nanoparticle homogeneous immunoassay based on Au nanoparticle tagging was proposed for CA19-9 determination, with a dynamic range from 6.25 to 400 U mL−1 in intensity mode and 6.25 to 100 U mL−1 in frequency mode. The limits of detection were 0.72 U mL−1 (intensity mode) and 0.84 U mL−1 (frequency mode). Accurate results were obtained without any washing and separation procedure, and the matrix effect was avoided by monitoring both the intensity and frequency signal obtained from single nanoparticles. The method was successfully applied to the serological evaluation of patients. The results were well correlated with those measured by conventional clinical methods, demonstrating a promising foreground in the preoperative assessment of resectability and evaluation of disease recurrence.
研究领域:
肿瘤学
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医学诊断
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纳米技术
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生物化学
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DOI
高影响因子
CELLULOSE
·
2020
·Vol. 27
·期 6
·3287-3300
·
IF 4.21
Zhang Su-Feng,Li Hao,Hou Chen,Liu Li-Na,Wang Yang,Zhao Meng-Ke,Liang Chen
Abstract The treatment of dyes in wastewater is important to solve environmental problems. Advanced oxidation processes has been proved to be an effective treatment. In this work, a novel nanocomposite catalyst of ZIF-9@Fe 3 O 4 (cobalt-containing zeolitic imidazolate framework-9 coated Fe 3 O 4 nanocomposite) modified reduced graphite oxide (RGO) was prepared for the first time and coded as ZIF-9@CA-Fe 3 O 4 /RGO. Then, ZIF-9@CA-Fe 3 O 4 /RGO was immobilized on a cellulose membrane to obtain a composite membrane, which was used as a composite catalyst for activating peroxymonosulfate to degrade methylene blue (MB). The results demonstrated that the composite membrane could efficiently degrade approximately 96% of MB in 9 min without adjusting the initial pH and maintain good catalytic activity even after seven cycles. Furthermore, the composite membrane can be easily separated from the solution at the end of the reaction. This work indicates that the composite membrane has a broad application prospect in industrial applications. Graphic abstract
研究领域:
环境科学
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材料科学
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产品关联
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Chuanlu Lin,Yiqiang Hu,Ze Lin,Longyu Du,Yixin Hu,Lizhi Ouyang,Xudong Xie,Peng Cheng,Jiewen Liao,Li Lu,Ruiyin Zeng,Ping Xia,Zhiyong Hou,Guohui Liu,Hankun Hu
Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca 2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.
研究领域:
药理学
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生物医学工程
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细胞生物学
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2025
·
IF 3.6
Haoyang Liu,Hailiang Xing,Peilan Yu,Yanjie Wang,Jia-Lei Yan,Junyang Liu,Min Wang
A facile copper-catalyzed, base-controlled cyclization reaction has been developed for the synthesis of 9-membered cycloalkyne and 6-membered heterocycle sultams under mild conditions. This protocol utilizes a copper-catalyzed intramolecular A3 (alkyne–aldehyde–amine) coupling reaction to efficiently synthesize 9-membered cycloalkyne sultams in yields up to 90%. Alternatively, by substituting NaHCO3 with DBU, the protocol achieves selective deprotection of the N-propargyl group, thereby facilitating the formation of 6-membered heterocyclic sultams, also in high yields.
研究领域:
有机化学
·
合成化学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-9
·
IF 6.1
Zheng Rongji,Guan Tian,Hong Chaoqun,Yao Yao,Fang Yutong,Huang Wei,Chen Chunfa,Zeng Huancheng,Huang Jiman,Lin Hui,Chen Bingfeng,Zhang Rendong,Chen Dongmei,Ding Zhechun,Zeng Haoyu,Wu Jundong
ObjectivesSTAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs.Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway.Conclusion sIn this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.
研究领域:
肿瘤学
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Viruses-Basel
·
2022
·Vol. 14
·期 11
·2431
·
IF 5.818
Jing Zheng,Wenyuan Chen,Hao Xiao,Fan Yang,Xiaowu Li,Jingdong Song,Lingpeng Cheng,Hongrong Liu
GP4, a newRalstonia solanacearumphage, is a short-tailed phage. Few structures ofRalstonia solanacearumphages have been resolved to near-atomic resolution until now. Here, we present a 3.7 Å resolution structure of the GP4 head by cryo-electron microscopy (cryo-EM). The GP4 head contains 540 copies of major capsid protein (MCP) gp2 and 540 copies of cement protein (CP) gp1 arranged in an icosahedral shell with a triangulation number T = 9. The structures of gp2 and gp1 show a canonical HK97-like fold and an Ig-like fold, respectively. The trimeric CPs stick on the surface of the head along the quasi-threefold axis of the icosahedron generating a sandwiched three-layer electrostatic complementary potential, thereby enhancing the head stability. The assembly pattern of the GP4 head provides a platform for the further exploration of the interaction betweenRalstonia solanacearumand corresponding phages.Keywords:Ralstonia solanacearumphage;icosahedral head;triangulation number T = 9;trimeric CP;Cryo-EM
研究领域:
病毒学
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结构生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Lei Tian,Mengni Pan,Cuiping Ye,Hongbo Hao,Wenying Li
Phenanthrene (Phe) and fluorene (Flu) are crucial chemical intermediates with applications in materials, medicine, and pesticides. However, conventional separation methods struggle to effectively isolate phenanthrene from fluorene due to their similar physical properties. To address this challenge, a reaction–separation coupling technique was employed to convert fluorene into 9-fluorenone (9-Fluo), followed by the separation of phenanthrene from 9-fluorenone using solvent-cooling crystallization. Initially, the relative solubilities of phenanthrene and 9-fluorenone in 2072 solvents were calculated using COSMO-RS for preliminary screening. Among various conventional short-chain aliphatic alcohols and low-carbon saturated hydrocarbons, methanol, and cyclohexane were identified as the most effective solvents based on their solubility selectivity (SS). The molecular interactions between phenanthrene or 9-fluorenone and these solvents were analyzed using theoretical methods such as σ-potential/profile, infinite dilution activity coefficients in COSMO-RS, and Hansen solubility parameters, with further confirmation from FTIR tests. The optimal liquid–solid ratios were determined using both phase diagram measurements and solubility calculations. The reaction conversion of fluorene to 9-fluorenone was complete regardless of the raw material used. Phenanthrene and 9-fluorenone were effectively separated using methanol and cyclohexane with optimum liquid–solid mass ratios of 1.6:1 and 2.8:1, respectively. In the model mixture, the contents of phenanthrene and 9-fluorenone exceeded 98 wt%, with yields above 91 wt%. For anthracene residue, the content of 9-fluorenone reached 93.98 wt% with a yield of 84.52 wt%, while its content was only 76.58 wt% due to the accumulation of other components in phenanthrene.
研究领域:
化学工程
·
材料科学
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产品关联
DOI
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 2
·123
·
IF 6.6
Qian Zhou,Xu-Nian Wu,Wei-Hao Luo,Qing-Hua Huang,Ling-Ling Feng,Yinuo Wu,Chen Zhang
Alzheimer’s disease (AD) is a widely recognized type of dementia that leads to progressive cognitive decline and memory loss, affecting a significant number of people and their families worldwide. Given the multifactorial nature of AD, multitarget-directed ligands (MTDLs) hold promise in developing effective drugs for AD. Phosphodiesterase-9 (PDE9) is emerging as a promising target for AD therapy. In this study, by combining a PDE9 inhibitor C33 with the antioxidant melatonin, we designed and discovered a series of pyrazolopyrimidinone derivatives that simultaneously inhibit PDE9 and possess antioxidant activities. Molecular docking, together with dynamics simulations, were applied to accelerate compound design and reduce synthetic work. Four out of the 14 compounds were validated as effective PDE9 inhibitors with comparable antioxidant activity. Notably, compounds 17b and 17d demonstrated IC 50 values of 91 and 89 nM against PDE9, respectively, with good antioxidant activities (ORAC (Trolox) of 2.00 and 2.60). This work provides a new approach for designing MTDLs for the treatment of AD and offers insights for further structural modifications of PDE9 inhibitors with antioxidant capacities.
研究领域:
神经科学
·
药物化学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）