Science China-Chemistry
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2018
·Vol. 61
·期 4
·412-417
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IF 4.448
Si Yanyan,Liang Lujun,Tang Shan,Qi Yunkun,Huang Yong,Liu Lei
Ubiquitin (Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub (Ub 3 11/48 (S–S)), the first example of an isopeptide mimic for the branched Ub chains, which have recently emerged as an interesting category of Ub modifications. Our strategy comprised the E1-dependent synthesis of the Ub conjugate of aminoethanethiol, followed by disulfide formation with Ub(K11C, K48C). The structure of the synthetic isopeptide bond mimics was verified by the crystal structure of Ub 3 11/48 (S–S). Deubiquitination and pulldown assays indicated that the synthetic Ub 3 11/48 (S–S) could be hydrolyzed by linkage-specific deubiquitinases (K11-specific Cezanne and K48-specific OTUB1), and recognized by proteasomal ubiquitin receptor S5a.
研究领域:
生物化学
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分子生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2016
·
IF 2.857
Qin Li,Xiaobo Huang,Shaochen Li,Jingchun Ma,Min Lv,Hui Xu
A total of 20 esters of fraxinellone C4/10-oxime were synthesized and determined by melting points, optical rotation, infrared spectra, proton nuclear magnetic resonance spectra, and high-resolution mass spectrometry spectra. Two steric configurations of compounds 7i and 8i were unambiguously confirmed by X-ray crystallography. Additionally, their pesticidal activities were assessed on two typical lepidopteran pests, Mythimna separata Walker and Plutella xylostella Linnaeus. Generally, all compounds exhibited less potent oral toxicity than toosendanin against third-instar larvae of P. xylostella. However, all compounds showed the growth inhibitory property against early third-instar larvae of M. separata. Notably, compounds 7m, 8b, 8k, 9, and 11 displayed more potent pesticidal activity than toosendanin. This demonstrated that introducing the C-4 carbonyl or oxime group on fraxinellone resulted in more promising derivatives than those bearing a C-10 carbonyl or oxime substituent.
研究领域:
植物化学
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农药科学
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有机化学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Xiaoqin Liu,Xufeng Zang,Xiaoli Yin,Wuying Yang,Jinxiang Huang,Jianping Huang,Chunxian Yu,Chunshan Ke,Yanping Hong
Combining two bioactive moieties by covalent bond into a novel single hybrid biological entity in view of the principle of active splicing, twenty-two C28-modified derivatives of pentacyclic dihydroxytriterpene carboxylic acids with saturated nitrogen heterocycle segments (i.e. 1-deoxynojirimycin or piperazines) have been synthesized. The inhibitory activities of all final target compounds on α-glucosidase were evaluated in vitro . The results of α-glucosidase inhibition assay indicate that some derivatives (e.g. 4b : IC 50 = 1468.4 µM; 12b : IC 50 = 499.6 µM 12c : IC 50 = 768.5 µM, 13c : IC 50 = 819.2 µM) show superior inhibitory activity in α-glucosidase than that of the precursor maslinic acid (IC 50 = 2540.6 µM) or corosolic acid (IC 50 = 1363.7 µM), in which compound 12b (IC 50 = 499.6 µM) possesses stronger inhibitory activity than that of acarbose (IC 50 = 606 µM). In addition, the result of enzyme kinetics study reveals that the inhibitory mechanism of the compound 12b is non-competitive inhibition and the inhibition constant K i is 570 µM. The binding interaction between compounds with α-glucosidase are predicted by molecular docking simulation.
研究领域:
药理学
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有机化学
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生物化学
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2020
·Vol. 17
·期 12
·e2000763
·
IF 2.039
Zhiyan Liu,Jiangping Cao,Xiaoting Yan,Wanqing Cheng,Xiaoguang Wang,Ruige Yang,Yong Guo
Many phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products-based fungicides, a series of thirty-one sarisan attached 3-phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi ( B. cinerea , C. lagenarium , A. solani , F. solani , and F. graminearum ). Among all title sarisan derivatives, compounds IV2 , IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad-spectrum and more potent antifungal activity against A. solani , F. solani , and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2 , IV14 and IV23 also displayed relative low toxicity on normal NRK-52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection. Graphical
研究领域:
植物病理学
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药物化学
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农业科学
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DOI
高影响因子
ZEITSCHRIFT FUR NATURFORSCHUNG SECTION B-A JOURNAL OF CHEMICAL SCIENCES
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2021
·
IF 1.047
Chun Yang,Lili Song,Zhong Miao,Lingyun Jiang,Ting Li,Xiaoyan Zhi,Xiaojuan Hao,Hui Cao
To explore candidate fungicides from plant secondary metabolites, 16 novel obovatol-type phenazine derivatives were semi-synthesized from obovatol isolated from the leaves of Magnolia obovata Thunb. The antifungal activity of synthesized compounds was investigated in vitro against four phytopathogenic fungi using the spore germination method. The bioassay results showed that eight derivatives ( 8b , 8g , 8h – k , 8i′ , and 8k′ ) exhibited better antifungal activity against Fusarium solani than two positive controls, especially compounds 8b (IC 50 = 64.61 μg mL −1 ) and 8i′ (IC 50 = 79.97 μg mL −1 ) showed pronounced inhibition of spore germination activity against F. solani . They could be used as lead compounds for further structural optimization. Additionally, the preliminary structure-activity relationships (SARs) illustrated that the introduction of a benzene ring monosubstituted with electron-withdrawing groups into the obovatol scaffold could lead to potentially antifungal compounds.
研究领域:
植物化学
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药物化学
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真菌学
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DOI
高影响因子
PEST MANAGEMENT SCIENCE
·
2020
·Vol. 76
·期 8
·2711-2719
·
IF 3.75
Xingan Cheng,Huiqing He,Wen-Xiong Wang,Fangyun Dong,Hanhui Zhang,Jingmin Ye,Chuncan Tan,Yuehua Wu,Xiaojing Lv,Xuhong Jiang,Xiangjing Qin
BACKGROUND Matrine is an important traditional plant-derived insecticide with broad-spectrum activity. However, due to its moderate activity, matrine is mainly applied in combination with other pesticides. In order to discover new potential natural-product-based crop protection agents, a series of matrine derivatives characterized by cyclohexylamine group were synthesized to screen their insecticidal activity against seven typically agricultural pests. RESULTS The structural configurations of compounds were characterized by IR, 1 H NMR, 13 C NMR, MS and XRD, with the pure yields of 42%, 65% and 71%, respectively. Although all compounds showed poor insecticidal activity against five lepidoptera pests, the compounds 2 and 4 displayed remarkable insecticidal activities against Lipaphis erysimi and Mulberry Root-Knot Nematode with a concentration-dependent manner within 0.5~1.5 mg/ mL. Compared with matrine (60%), compounds 2 and 4 exhibited potent insecticidal activities against L. erysimi , with a corrected mortality of 83.3% and 89.7%, respectively. They also showed excellent control effects on Mulberry Root-Knot Nematode , with corrected mortality as high as 88% and 80%, respectively. CONCLUSION All four synthesized matrine derivatives showed poor insecticidal activity against five lepidoptera pests, but the compounds 2 and 4 exhibited much stronger insecticidal activities against L. erysimi and Mulberry Root-Knot Nematode than matrine. Combined with the structural characteristics of compounds 1~4, we conclude that 4-methylcyclohexylamine, not the carbon disulfide group or cyclohexylamine group alone, mainly contributed to the improvement of insecticidal activities of matrine derivatives against these two agricultural pests. This work provides a direction and foundation for structural optimization of the matrine pesticides in the future. © 2020 Society of Chemical Industry
研究领域:
植物化学
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农业科学
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有机化学
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PubMed
高影响因子
FITOTERAPIA
·
2019
·
IF 2.431
Zhong-Sheng Wang,Wei Chen,Hai-Yue Jiang,Feng Gao,Xian-Li Zhou
Four new C 19 -diterpenoid alkaloids brevicanines A–D ( 1–4 ) with rotameric phenomenon were isolated from Aconitum brevicalcaratum . They all possessed an unusual axial chiral phenyl-quinazoline side chain and their structures were elucidated by extensive spectroscopic analysis and chemical methods. Meanwhile, brevicanines A and B were semi-synthesized from their parent compound scaconine to further confirm their structures. Variable-temperature NMR spectroscopy was also used to investigate the atropisomers of brevicanine A, in which two sets of signals in 1 H NMR spectra were observed at room temperature and coalesced over 140 °C. It's the first time to determine the atropisomeric preference of diterpenoid alkaloids.
研究领域:
植物化学
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天然产物化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Dongliang Guan,Jian Li,Feifei Chen,Jiaqi Li,Xiaolei Bian,Yue Yu,Xinxin Feng,Lefu Lan,Wei Huang
Wide-spread use of daptomycin unavoidably resulted in the emergence of daptomycin-resistant pathogens. In the hunt for more active daptomycin derivatives through medicinal chemistry studies, we established a concise semisynthetic approach to modify the L-Kyn13 on daptomycin specifically and effectively. Here, 19 novel derivatives with certain diversity were designed and synthesized to perform a comprehensive SAR study on this underestimated position. The optimal compound, termed “hexakynomycin”, as the new generation of daptomycin-based antibiotic candidate exhibited 4->125-fold higher activity against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE), including daptomycin-resistant strains, compared with that of daptomycin. Greater membrane binding capacity rendered hexakynomycin better activity and special antibiotic property. Hexakynomycin also demonstrated a better pharmacokinetic profile, good safety features and good pharmacodynamics properties. This work provided an effective modification strategy aiming at daptomycin which provided significant insights and showed great promise for the next generation of daptomycin derivatives.
研究领域:
医药化学
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微生物学
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感染病学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Ruifang Bai,Yan Cui,Lanxin Luo,Danbing Yuan,Zongmin Wei,Weichao Yu,Baoshan Sun
Polymeric procyanidins (PPCs) were the major constituents of procyanidins, while they have poor bioactivity. To better utilize PPCs, a semisynthetic approach for converting PPCs to oligomeric procyanidins (OPCs) was proposed. Grape seed PPCs were simultaneously reacted with catechin (C) and epicatechin (EC) under acid condition. Combining response surface methodology (RSM) and single-factor experiments, an optimized semisynthetic condition was confirmed with the ratio of PPCs with C and EC of 1:1:1, temperature of 40 °C, reaction time of 20 min and 0.1 M methanolic HCl. High-speed counter-current chromatography (HSCCC) was adopted to obtain three fractions from semisynthetic products and preparative-HPLC was used to isolate individual procyanidins. Thirteen B-type procyanidins including monomers, dimers and trimers were got with high yield of 0.8–17.8 mg from 200 mg semisynthetic products and high purity over 91%. The developed semisynthesis combined with separation method was efficient to obtain individual OPCs in preparative scale.
研究领域:
植物化学
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天然产物化学
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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 ORGANIC CHEMISTRY
·
2019
·
IF 4.745
Jian Fan,Yinshan Ye,Guochao Chu,Zhongping Zhang,Yao Fu,Yi-Ming Li,Jing Shi
Ubiquitin (Ub)-based fluorescent reagents are crucial to explore the activity of deubiquitinases (DUBs). Ub-Rho110-G is one of the preferred tools, whereas the current synthetic route is time-consuming. Here, we report a new semisynthetic strategy to produce Ub-Rho110-G through direct aminolysis of Boc-protected Ub-Mesna using bisglycyl-rhodamine 110. We also applied this strategy to synthesize active SUMO2-Rho110-G for the first time. Biochemical analysis demonstrated that semisynthetic Ub or SUMO-Rho110-G can be effectively used for the detection of the activity of DUBs or SUMO-specific enzymes.
研究领域:
生物化学
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分子生物学
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蛋白质组学
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DOI
PubMed
高影响因子
Bioresources and Bioprocessing
·
2016
·Vol. 3
·期 1
·1-8
·
IF 0
Zhang Xiao-Li,Zong Min-Hua,Li Ning
Enzymatic approaches have become promising alternatives to chemical methods for the production of semi-synthetic β-lactam antibiotics. In this work, enzymatic synthesis of N-bromoacetyl-7-aminocephalosporanic acid (N-bromoacetyl-7-ACA), the key intermediate for the production of cefathiamidine, was reported for the first time.Of the immobilized penicillin acylases (PAs) tested, PGA-750 was the best biocatalyst. Optimization of the biocatalytic process was conducted. The optimal acyl donor, molar ratio of acyl donor to 7-ACA, pH, temperature, 7-ACA concentration, and enzyme dosage were methyl bromoacetate, 3, 7.5, 20 °C, 50 mmol/L and 4 U/mL, respectively. Under the optimal conditions, enzymatic N-acylation of 7-ACA with methyl bromoacetate afforded the desired product with the yield of 85% in 2 h, where the synthesis/hydrolysis (S/H) ratio was approximately 1.5. The immobilized enzyme PGA-750 exhibited good operational stability, and the relative yields of approximately 90% and 63% were achieved, respectively, when it was reused in 7th and 11th batch.An enzymatic approach to N-bromoacetyl-7-ACA, the key intermediate for the industrial production of cefathiamidine, has been developed successfully in a fully aqueous medium. The present work may open up a novel opportunity for the production of cefathiamidine through a simple and green process.
研究领域:
生物化学
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制药工程
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酶催化
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DOI
PubMed
Antibiotics-Basel
·
2019
·Vol. 8
·期 2
·45
·
IF 2.921
Bernardo Ribeiro da Cunha,Luís P. Fonseca,Cecília R. C. Calado
Given the increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures—platforms—that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines. During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.Keywords:antibiotic discovery platforms;drug screening;semi-synthesis;fully synthetic antibiotics;genomics;proteomics;metabolomics;lipidomics;metagenomics
研究领域:
药理学
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微生物学
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基因组学
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生物信息学
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DOI
PubMed
高影响因子
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