CHEMICO-BIOLOGICAL INTERACTIONS
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2023
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IF 5.1
Yun Yang,Yuan Xiong,Guanghao Zhu,Mengru Sun,Kun Zou,Yitian Zhao,Yong Zhang,Zhijian Xu,Yiming Li,Weiliang Zhu,Qi Jia,Bo Li,Guangbo Ge
Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC 50 = 1.66 μM) and excellent selectivity over hCES1A (IC 50 > 100 μM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K i value of 1.035 μM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
研究领域:
药理学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
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2023
·Vol. 45
·期 3
·2300510
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IF 4.6
Kangkang Tao,Gaohui Sun,Shuai Zhang,Jun Wang,Rongrong Chen,Shihui Han
Polyimide (PI) film with hydrophilic greatly limits their application in the field of microelectronic device packaging. A novel hydrophobic PI film with sag structure and improved mechanical properties is prepared relying on the reaction between anhydride-terminated isocyanate-based polyimide (PIY) containing a seven-membered ring structure and the amino-terminated polyamide acid (PAA) via multi-hybrid strategy, this work named it as hybrid PI film and marked it as PI-PIY-X. PI-PIY-30 showed excellent hydrophobic properties, and the water contact angle could reach to 102°, which is 20% and 55% higher than simply PI film and PIY film, respectively. The water absorption is only 1.02%, with a decrease of 49% and 53% compared with PI and PIY. Due to that the degradation of seven-membered ring and generation of carbon dioxide led to the formation of sag structure, the size of sag structures is ≈16.84 and 534.55 nm for in-plane and out-plane direction, which are observed on surface of PI-PIY-30. Meanwhile, PI-PIY-30 possessed improved mechanical properties, and the tensile strength is 109.08 MPa, with 5% and more than 56% higher than that of pure PI and PIY film, showing greatly application prospects in the field of integrated circuit.
研究领域:
材料科学
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微电子学
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产品关联
DOI
PubMed
高影响因子
ACS Synthetic Biology
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2019
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IF 5.571
Yan Li,Mengyuan Wang,Qianjing Zhao,Xiaolin Shen,Jia Wang,Yajun Yan,Xinxiao Sun,Qipeng Yuan
Tropone is a seven-membered ring nonbenzenoid aromatic compound. It is the core structure of tropolonoids, which have various biological activities. In this study, a hybrid tropone biosynthetic pathway was designed by connecting phenylacetic acid (PAA) degradation with its biosynthesis and reconstituted in Escherichia coli. To simplify pathway construction and optimization, the use of E. coli endogenous genes was maximized and only three exogenous genes were employed. The entire pathway was divided into four modules: the endogenous shikimate pathway module, the hybrid PAA biosynthetic module, the endogenous PAA catabolic module and the heterogeneous tropone biosynthetic module. Efficiency of the PAA catabolic module was enhanced using PAA consumption rate as the indicator. Then, a single point mutation was introduced to inactivate the ALDH domain of PaaZ and the carbon flow was redirected toward tropone synthesis. Assembly of the full pathway led to de novo tropone production with the best titer of 65.2 ± 1.4 mg/L in shake flask experiment. This study provides a potential alternative for sustainable production of tropone and its derivatives.
研究领域:
合成生物学
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微生物工程
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产品关联
DOI
PubMed
高影响因子
TETRAHEDRON
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2013
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IF 2.803
Kun Tong,Jinchang Tu,Xueyong Qi,Min Wang,Yanjie Wang,Haizhen Fu,Charles U. Pittman,Aihua Zhou
Five- and seven-membered sultam derivatives were conveniently synthesized via intra- or intermolecular Michael additions and an improved vinyl sulfonamide Baylis–Hillman reaction. Two different cyclization pathways were explored for the oxa-Michael reaction. A good solvent was discovered for an otherwise sluggish ketone-type Baylis–Hillman reaction in which vinyl sulfonamide ketones were used as the precursors. Furthermore, a strong base caused vinyl sulfonamide ketones to undergo 5- endo - trig intramolecular cyclizations, which are disfavored according to Baldwin's rule. Finally Baylis–Hillman reaction products were used as scaffolds for diversity-oriented sultam syntheses.
研究领域:
有机化学
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合成化学
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产品关联
DOI
高影响因子
Frontiers in Plant Science
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2022
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IF 6.627
Lei Wenli,Song Yuyang,Long Ai,Que Yanyan,He Shuzhong,Zhong Hang,Chen Yang
The medicinal plants were wildly library of natural products in drug discovery. The most active molecules with seven-membered rings skeleton represent a challenge for construction. A stereoselectivity (4 + 3) cycloadditions between allenyl ethers and substituted furans induced by chiral auxiliaries has been investigated. And the results showed significant stereoselectivities and regioselectivities. The optical cycloadducts with an oxygen-substituted seven-membered ring framework were generated by removing chiral auxiliaries under acidic conditions. The antiproliferative activity of the novel compounds displayed moderate antiproliferative effects toward T47D cells.
研究领域:
有机化学
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药物化学
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癌症研究
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DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
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2015
·Vol. 19
·期 3
·447-458
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IF 1.896
Niu Ben,Xie Ping,Wang Min,Wang Yanjie,Zhao Wannian,Pittman Charles U.,Zhou Aihua
A series of seven- and eight-membered ring – N,O –, – N,N –, and – N,S –sultams were effectively synthesized via tandem reactions involving oxa-, aza-, and thia-Michael addition to vinyl sulfonamides. These reactions are summarized here since they enrich current synthetic methodologies for sultams and provide a good example of sultam diversity-oriented synthesis. All reactions proceeded under relatively mild and environmentally friendly conditions, and all these reactions are quite suitable for the rapid preparation of sultam compound libraries, which are valuable for biological activity explorations.
研究领域:
有机化学
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合成化学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）