Design, synthesis and insecticidal activity of novel 1,1-dichloropropene derivatives
作者：
Li, Jun;Wang, Zhen-Yu;Wu, Qiong-You;Yang, Guang-Fu
* （ 期刊：
Pest Management Science ,2015年71(5):694-700 ISSN：1526-498X
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Li, Jun; Wang, Zhen-Yu; Wu, Qiong-You] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
1-dichloropropene;insecticide;pyridalyl;heterocycle
摘要：
BACKGROUNDPyridalyl is a highly active insecticide against lepidopterous larvae, with a novel chemical structure not related to any other existing insecticide. To discover new pyridalyl analogues with high activity against resistant pests, a series of 1,1-dichloropropene derivatives bearing structurally diverse substituted heterocycle rings in place of the pyridine ring of pyridalyl were designed and synthesised. RESULTSAll of the title compounds were confirmed by H-1 NMR, C-13 NMR and high-resolution mass spectra. Two representative compounds (Ic and IIa) were further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed good insecticidal activity against Prodenia litura. Further determination of LD50 values and field trials identified compound IIa as the most promising candidate, which produced a much better 14 day control effect against diamondback moths and longer duration of efficacy than pyridalyl, indicating its potential for further development as a new insecticide for the control of lepidopteran insects. CONCLUSIONCompound IIa has great potential for further development as a new insecticide for the control of lepidopteran insects. (c) 2014 Society of Chemical Industry
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Design, synthesis and herbicidal activity of novel quinazoline-2,4-diones as 4-hydroxyphenylpyruvate dioxygenase inhibitors
作者：
Wang, Da-Wei;Lin, Hong-Yan;Cao, Run-Jie;Ming, Ze-Zhong;Chen, Tao;...
期刊：
Pest Management Science ,2015年71(8):1122-1132 ISSN：1526-498X
通讯作者：
Yang, Wen-Chao
作者机构：
[Yang, Guang-Fu; Yang, Wen-Chao; Ming, Ze-Zhong; Chen, Tao; Wang, Da-Wei; Lin, Hong-Yan; Cao, Run-Jie; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin, Peoples R China.;[Yang, Wen-Chao] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词：
herbicide;4-hydroxyphenylpyruvate dioxygenase;quinazoline-2;4-dione;structure-activity relationship;weed control
摘要：
BACKGROUND4-Hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27) has been identified as one of the most promising target sites for herbicide discovery. To discover novel HPPD inhibitors with high herbicidal activity and improved crop selectivity, a series of novel triketone-containing quinazoline-2,4-dione derivatives possessing a variety of substituents at the N-1 position of the quinazoline-2,4-dione ring were designed and synthesised. RESULTSThe results of in vitro tests and greenhouse experiments indicated that some analogues showed good HPPD inhibitory activity, with promising broad-spectrum herbicidal activity at a rate of 150g AI ha(-1). Most surprisingly, compound 11h, 1-ethyl-6-(2-hydroxy-6-oxocyclohex-1-enecarbonyl)-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione, showed the highest HPPD inhibition activity, with a K-i value of 0.005 M, about 2 times more potent than mesotrione (K-i=0.013 M). Further greenhouse experiments indicated that compounds 11d and 11h displayed strong and broad-spectrum post-emergent herbicidal activity even at a dosage as low as 37.5g AI ha(-1), which was superior to mesotrione. More importantly, compounds 11d and 11h were safe for maize at a rate of 150g AI ha(-1), and compound 11d was safe for wheat as well. CONCLUSIONThe present work indicated that the triketone-containing quinazoline-2,4-dione motif could be a potential lead structure for further development of novel herbicides. (c) 2014 Society of Chemical Industry
语种：
英文
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Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein
作者：
Hao, Ge-Fei
* ;Xu, Wei-Fang;Yang, Sheng-Gang;Yang, Guang-Fu
（ 期刊：
Scientific Reports ,2015年5(1):15568 ISSN：2045-2322
通讯作者：
Hao, Ge-Fei
作者机构：
[Yang, Guang-Fu; Xu, Wei-Fang; Yang, Sheng-Gang; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.
通讯机构：
[Hao, Ge-Fei] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
摘要：
Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation.
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英文
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Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors
作者：
Xu, Yu-Ling;Lin, Hong-Yan;Ruan, Xu;Yang, Sheng-Gang;Hao, Ge-Fei;...
期刊：
European Journal of Medicinal Chemistry ,2015年92:427-438 ISSN：0223-5234
通讯作者：
Yang, Wen-Chao
作者机构：
[Yang, Guang-Fu; Xu, Yu-Ling; Yang, Sheng-Gang; Ruan, Xu; Yang, Wen-Chao; Lin, Hong-Yan; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol Minist Educ, Wuhan 430079, Peoples R China.
关键词：
4-Hydroxyphenylpyruvate dioxygenase;Benzimidazolone;Inhibitors;Type I tyrosinemia
摘要：
4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia. Inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC), has been available for clinical use so far. In the present study, a series of novel pyrazole-benzimidazolone hybrids were designed, synthesized and evaluated as potent human HPPD inhibitors. Most of the new compounds displayed significant inhibitory activity against the recombinant human HPPD. Moreover, compound 9l was identified as the most potent candidate with IC50 value of 0.021 mM against recombinant human HPPD, about 3-fold more potent than NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further developed for the treatment of type I tyrosinemia. © 2015 Elsevier Masson SAS.
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英文
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Iron-catalyzed hydrogenation of bicarbonates and carbon dioxide to formates
作者：
Zhu, Fengxiang
* ;Zhu-Ge, Ling;Yang, Guangfu
（ ;Zhou, Shaolin
期刊：
ChemSusChem ,2015年8(4):609-612 ISSN：1864-5631
通讯作者：
Zhu, Fengxiang
作者机构：
[Yang, Guangfu; Zhou, Shaolin; Zhu-Ge, Ling; Zhu, Fengxiang] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;[Zhou, Shaolin] CCNU uOttawa Joint Res Ctr, Wuhan, Peoples R China.;[Zhu, Fengxiang] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Zhu, Fengxiang] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
carbon dioxide;formates;homogeneous catalysis;hydrogenations;iron
摘要：
The catalytic hydrogenation of carbon dioxide and bicarbonate to formate has been explored extensively. The vast majority of the known active catalyst systems are based on precious metals. Herein, we describe an effective, phosphine-free, airand moisture-tolerant catalyst system based on Knölker's iron complex for the hydrogenation of bicarbonate and carbon dioxide to formate. The catalyst system can hydrogenate bicarbonate at remarkably low hydrogen pressures (1-5 bar). © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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英文
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Synthesis and antifungal activity of novel streptochlorin analogues
作者：
Zhang, Ming-Zhi;Chen, Qiong* ;Xie, Cai-Hong;Mulholland, Nick;Turner, Sarah;...
期刊：
European Journal of Medicinal Chemistry ,2015年92:776-783 ISSN：0223-5234
通讯作者：
Chen, Qiong
作者机构：
[Yang, Guang-Fu; Xie, Cai-Hong; Zhang, Ming-Zhi; Chen, Qiong] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Irwin, Dianne; Turner, Sarah; Clough, John; Gu, Yu-Cheng; Mulholland, Nick] Syngenta, Jealotts Hill Int Res Ctr, Bracknell RG42 6EY, Berks, England.
通讯机构：
[Chen, Qiong] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词：
Antifungal activity;Natural product;Streptochlorin;Structure-activity relationships;Synthesis
摘要：
Streptochlorin, first isolated as a new antibiotic in 1988 from the lipophilic extracts of the mycelium of a Streptomyces sp, is an indole natural products with a variety of biological activities. Based on the methods developed for the synthesis of pimprinine in our laboratory, we have synthesized a series of indole-modified streptochlorin analogues and measured their activities against seven phytopathogenic fungi. Some of the analogues displayed good activity in the primary assays, and the seven compounds 10b, 10c, 11e, 13e, 21, 22c and 22e (shown in Figure 1) were identified as the most promising candidates for further study. Structural optimization is still ongoing with the aim of discovering synthetic analogues with improved antifungal activity. © 2015 Elsevier Masson SAS.
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英文
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A review on recent developments of indole-containing antiviral agents
作者：
Zhang, Ming-Zhi;Chen, Qiong
* ;Yang, Guang-Fu
（ 期刊：
European Journal of Medicinal Chemistry ,2015年89:421-441 ISSN：0223-5234
通讯作者：
Chen, Qiong
作者机构：
[Yang, Guang-Fu; Zhang, Ming-Zhi; Chen, Qiong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Chen, Qiong] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
Indole;Antiviral activity;Entry and fusion inhibitor;Reverse transcriptase inhibitor;Integrase inhibitor;Protease inhibitor;Polymerase inhibitor;Natural product
摘要：
Indole represents one of the most important privileged scaffolds in drug discovery. Indole derivatives have the unique property of mimicking the structure of peptides and to bind reversibly to enzymes, which provide tremendous opportunities to discover novel drugs with different modes of action. There are seven indole-containing commercial drugs in the Top-200 Best Selling Drugs by US Retail Sales in 2012. There are also an amazing number of approved indole-containing drugs in the market as well as compounds currently going through different clinical phases or registration statuses. This review focused on the recent development of indole derivatives as antiviral agents with the following objectives: 1) To present one of the most comprehensive listings of indole antiviral agents, drugs on market or compounds in clinical trials; 2) To focus on recent developments of indole compounds (including natural products) and their antiviral activities, summarize the structure property, hoping to inspire new and even more creative approaches; 3) To offer perspectives on how indole scaffolds as a privileged structure might be exploited in the future. © 2014 Elsevier Masson SAS.
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英文
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Discovery of N-benzoxazol-5-yl-pyrazole-4-carboxamides as nanomolar SQR inhibitors
作者：
Xiong, Li;Zhu, Xiao-Lei* ;Shen, Yan-Qing;Wishwa, Wickramabahu Kandergama Wasala Mudiyanselage;Li, Kui;...
期刊：
European Journal of Medicinal Chemistry ,2015年95:424-434 ISSN：0223-5234
通讯作者：
Zhu, Xiao-Lei
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Xiong, Li; Wishwa, Wickramabahu Kandergama Wasala Mudiyanselage; Shen, Yan-Qing; Li, Kui] Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.;[Zhu, Xiao-Lei] Cent China Normal Univ, Coll Chem, Luoyu Rd 152, Wuhan 430079, Peoples R China.
通讯机构：
[Zhu, Xiao-Lei] C;Cent China Normal Univ, Coll Chem, Luoyu Rd 152, Wuhan 430079, Peoples R China.
关键词：
Computational simulations;MM/PBSA;Molecular design;Pyrazole-carboxamides;Succinate-ubiquinone oxidoreductase
摘要：
Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1, complex II), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, has been identified as one of the most significant targets for pharmaceutical and agrochemical. Herein, with the aim of discovery of new antibacterial lead structure, a series of N-benzoxazol-5-yl-pyrazole-4-carboxamides were designed, synthesized, and evaluated for their SQR inhibitory effects. Very promisingly, one candidate (Ki Combining double low line 11 nM, porcine SQR) was successfully identified as the most potent synthetic SQR inhibitor so far. The further inhibitory kinetics studies revealed that the candidate is non-competitive with respect to the substrate cytochrome c and DCIP. Computational simulations revealed that the titled compounds have formed hydrogen bond with D-Y91 and B-W173 and the pyrazole ring formed cation- interaction with C-R46. In addition, in R1 position, -CHF2 group has increased the binding affinity and decreased the entropy contribution, while -CF3 group displayed completely opposite effect when bound with SQR. The results of the present work showed that N-benzoxazol-5-yl-pyrazole-4-carboxamide is a new scaffold for discovery of SQR inhibitors and worth further study. © 2015 Elsevier Masson SAS.
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英文
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Ametoctradin is a Potent Q(o) Site Inhibitor of the Mitochondria! Respiration Complex III
作者：
Zhu, Xiaolei;Zhang, Mengmeng;Liu, Jingjing;Ge, Jingming;Yang, Guangfu
* （ 期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2015年63(13):3377-3386 ISSN：0021-8561
通讯作者：
Yang, Guangfu
作者机构：
[Yang, Guangfu; Liu, Jingjing; Zhu, Xiaolei; Ge, Jingming; Zhang, Mengmeng] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guangfu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Guangfu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词：
ametoctradin;cytochrome bc1 complex;molecular docking;molecular dynamics
摘要：
Ametoctradin is a new Oomycete-specific fungicide under development by BASF. It is a potent inhibitor of the bc<inf>1</inf>complex in mitochondrial respiration. However, its detailed action mechanism remains unknown. In the present work, the binding mode of ametoctradin was first uncovered by integrating molecular docking, MD simulations, and MM/PBSA calculations, which showed that ametoctradin should be a Q<inf>o</inf>site inhibitor of bc<inf>1</inf>complex. Subsequently, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized to further understand the substituent effects on the 5- and 6-position of 1,2,4-triazolo[1,5-a]pyrimidine. The calculated binding free energies (ΔG<inf>cal</inf>) of newly synthesized analogues as Q<inf>o</inf>site inhibitors correlated very well (R<sup>2</sup>= 0.96) with their experimental binding free energies (ΔG<inf>exp</inf>). Two compounds (4a and 4c) with higher inhibitory activity against porcine SQR than ametoctradin were successfully identified. The structural and mechanistic insights obtained from the present study will provide a valuable clue for future designing of a new promising bc<inf>1</inf>inhibitor. ©2015 American Chemical Society.
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英文
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Understanding resistance mechanism of protoporphyrinogen oxidase-inhibiting herbicides: Insights from computational mutation scanning and site-directed mutagenesis
作者：
Hao, Ge-Fei;Tan, Ying;Xu, Wei-Fang;Cao, Run-Jie;Xi, Zhen* ;...
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2014年62(29):7209-7215 ISSN：0021-8561
通讯作者：
Xi, Zhen
作者机构：
[Yang, Guang-Fu; Xu, Wei-Fang; Tan, Ying; Cao, Run-Fie; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;[Xi, Zhen] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.
通讯机构：
[Xi, Zhen] N;Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
关键词：
PPO;resistance mechanism;computational mutation scanning;herbicide;mutagenesis
摘要：
The potential of protoporphyrinogen oxidase (PPO) to develop resistance against five PPO-inhibiting herbicides has been studied using computational mutation scanning (CMS) protocol, leading to valuable insights into the resistance mechanisms and structure-resistance relationship of the PPO inhibitors. The calculated shifts in the binding free energies caused by the mutations correlated very well with those derived from the corresponding experimental data obtained from site-directed mutagenesis of PPO, leading to valuable insights into the resistance mechanisms of PPO inhibitors. The calculated entropy change was related to the conformational flexibility of the inhibitor, which demonstrated that inhibitors with appropriate conformational flexibility may inhibit both the wild type and mutants simultaneously. The reasonable correlation between the computational and experimental data further validate that CMS protocol is valuable for predicting resistance associated with amino acid mutations on target proteins. ©2014 American Chemical Society.
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英文
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Pyrazolone–quinazolone hybrids: A novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors
作者：
Xu, Yu-Ling;Lin, Hong-Yan;Cao, Run-Jie;Ming, Ze-Zhong;Yang, Wen-Chao* ;...
期刊：
Bioorganic & Medicinal Chemistry ,2014年22(19):5194-5211 ISSN：0968-0896
通讯作者：
Yang, Wen-Chao
作者机构：
[Yang, Guang-Fu; Xu, Yu-Ling; Yang, Wen-Chao; Ming, Ze-Zhong; Lin, Hong-Yan; Cao, Run-Jie] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Peoples R China.
关键词：
Human HPPD inhibitors;Pyrazolone;Quinazolones;Type I tyrosinemia
摘要：
4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Kivalues of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation. © 2014 Elsevier Ltd. All rights reserved.
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英文
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Synthesis, In Vitro Protoporphyrinogen Oxidase Inhibition, and Herbicidal Activity of N-(Benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones and N-(Benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones
作者：
Wu, Qiong-You;Jiang, Li-Li;Zuo, Yang;Wang, Zhi-Fang;Xi, Zhen;...
期刊：
CHEMICAL BIOLOGY & DRUG DESIGN ,2014年84(4):431-442 ISSN：1747-0277
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Wu, Qiong-You; Jiang, Li-Li; Zuo, Yang; Wang, Zhi-Fang] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Xi, Zhen] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
benzothiazole hexahydro-1H-isoindole-1,3(2H)-dione;herbicidal activity;hexahydro-1H-isoindol-1-one;protoporphyrinogen oxidase
摘要：
Protoporphyrinogen oxidase (EC 1.3.3.4) is one of the most significant targets for a large family of herbicides. As part of our continuous efforts to search for novel protoporphyrinogen oxidase-inhibiting herbicides, N-(benzothiazol-5-yl)tetrahydroisoindole-1,3-dione was selected as a lead compound for structural optimization, leading to the syntheses of a series of novel N-(benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones (1a-o) and N-(benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones (2a-i). These newly prepared compounds were characterized by elemental analyses, 1H NMR, and ESI-MS, and the structures of 1h and 2h were further confirmed by X-ray diffraction analyses. The bioassays indicated that some compounds displayed comparable or higher protoporphyrinogen oxidase inhibition activities in comparison with the commercial control. Very promising, compound 2a, ethyl 2-((6-fluoro-5-(4,5,6,7-tetrahydro-1-oxo-1H-isoindol-2(3H)-yl)benzo[d]thiazol-2-yl)-sulfanyl)acetate, was recognized as the most potent candidate with Ki value of 0.0091 μm. Further greenhouse screening results demonstrated that some compounds exhibited good herbicidal activity against Chenopodium album at the dosage of 150 g/ha. © 2014 John Wiley & Sons A/S.
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英文
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Synthesis and Herbicidal Evaluation of Triketone-Containing Quinazoline-2,4-diones
作者：
Wang, Da-Wei;Lin, Hong-Yan;Cao, Run-Jie;Yang, Sheng-Gang;Chen, Qiong;...
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2014年62(49):11786-11796 ISSN：0021-8561
通讯作者：
Yang, Wen-Chao
作者机构：
[Yang, Guang-Fu; Yang, Sheng-Gang; Yang, Wen-Chao; Chen, Qiong; Wang, Da-Wei; Lin, Hong-Yan; Cao, Run-Jie; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.
关键词：
4-hydroxyphenylpyruvate dioxygenase;crop selectivity;herbicidal activity;quinazoline-2,4-dione;synthesis
摘要：
Exploring novel 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) inhibitors is one of the most promising research directions in herbicide discovery. To discover new triketone herbicides with broad-spectrum weed control as well as excellent crop selectivity, a series of (total 52) novel triketone-containing quinazoline-2,4-dione derivatives were synthesized and further bioevaluated. The greenhouse testing indicated that many of the newly synthesized compounds showed better or excellent herbicidal activity against broadleaf and monocotyledonous weeds at the dosages of 37.5-150 g of active ingredient (ai)/ha. The structure and activity relationship in this study indicated that the triketone-containing quinazoline-2,4-dione motif has possessed great impact on herbicide activity and may be used for further optimization. Among the new compounds, III-b and VI-a-VI-d displayed a broader spectrum of weed control than mesotrione. In addition, the compound III-b also demonstrated comparatively superior crop selectivity to mesotrione, thus possessing great potential for weed control in the field. © 2014 American Chemical Society.
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英文
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Activity of a novel strobilurin fungicide benzothiostrobin against Sclerotinia sclerotiorum
作者：
Xu, Congying;Hou, Yiping;Wang, Jianxin;Yang, Guangfu
（ ;Liang, Xiaoyu;...
期刊：
Pesticide Biochemistry and Physiology ,2014年115:32-38 ISSN：0048-3575
通讯作者：
Zhou, Mingguo
作者机构：
[Xu, Congying; Liang, Xiaoyu; Hou, Yiping; Zhou, Mingguo; Wang, Jianxin] Nanjing Agr Univ, Coll Plant Protect, Key Lab Pesticide, Nanjing 210095, Jiangsu, Peoples R China.;[Yang, Guangfu] Cent China Normal Univ, Coll Chem, Wuhan 430079, Hubei Province, Peoples R China.
通讯机构：
[Zhou, Mingguo] N;Nanjing Agr Univ, Coll Plant Protect, Key Lab Pesticide, Nanjing 210095, Jiangsu, Peoples R China.
关键词：
Benzothiostrobin;Biological activity;Oxygen consumption;Sclerotinia sclerotiorum
摘要：
Benzothiostrobin is a novel strobilurin fungicide. In this study, baseline sensitivity of Sclerotinia sclerotiorum (Lib.) de Bary to benzothiostrobin was determined using 100 strains collected during 2012 and 2013 from different geographical regions in Jiangsu Province of China, and the average EC50 value was 0.0218 ( +/- 0.0111)mu g/mL for mycelial growth. After benzothiostrobin treatment, hyphae were contorted with offshoot of top increasing and cell membrane permeability increased markedly, while sclerotial production and oxalic acid content significantly decreased. Benzothiostrobin strongly inhibited mycelial respiration within 12 h and the oxygen consumption of the mycelia could not be inhibited after 24 h. On detached rapeseed leaves, the protective and curative activity test of benzothiostrobin suggested that benzothiostrobin had good control efficiency against S. sclerotiorum, and protective activity was better than curative activity. These results will contribute to us evaluating the potential of the new strobilurin fungicide benzothiostrobin for management of diseases caused by S. sclerotiorum and understanding the mode of action of benzothiostrobin against S. sclerotiorum. (C) 2014 Elsevier Inc. All rights reserved.
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Computational and experimental insight into the molecular mechanism of carboxamide inhibitors of succinate-ubquinone oxidoreductase
作者：
Zhu, Xiao-Lei;Xiong, Li;Li, Hui;Song, Xin-Ya;Liu, Jing-Jing;...
期刊：
ChemMedChem ,2014年9(7):1512-1521 ISSN：1860-7179
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Xiong, Li; Liu, Jing-Jing; Song, Xin-Ya; Li, Hui] Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.;[Yang, Guang-Fu] Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
inhibitors;MM/PBSA;molecular docking;succinate dehydrogenase;succinate-ubiquinone oxidoreductase
摘要：
Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1), also known as mitochondrial respiratory complex II or succinate dehydrogenase (SDH), catalyzes the oxidation of succinate to fumarate as part of the tricarboxylic acid cycle. SQR has been identified as a novel target of a large family of agricultural fungicides. However, the detailed mechanism of action between the fungicides and SQR is still unclear, and the bioactive conformation of fungicides in the SQR binding pocket has not been identified. In this study, the kinetics of porcine SQR inhibition by ten commercial carboxamide fungicides were measured, and noncompetitive inhibition was observed with respect to succinate, DCIP, and cytochrome c, while competitive inhibition was observed with respect to ubiquinone. With the aim to uncover the binding conformation of these fungicides, molecular docking, molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations were then performed. The excellent correlation (r2=0.94) between the calculated (&Delta;Gcal) and experimental (&Delta;Gexp) binding free energies indicates that the obtained docking conformation could be the bioactive conformation. The acid moiety of carboxamide fungicides inserts into the ubiquinone binding site (Q-site) of SQR, forming van der Waals (vdW) interactions with C-R46, C-S42, B-I218, and B-P169, while the amine moiety extends to the mouth of the Q-site, forming vdW interactions with C-W35, C-I43, and C-I30. The carbonyl oxygen atom of the carboxamide forms hydrogen bonds with B-W173 and D-Y91. These findings provide valuable information for the design of more potent and specific inhibitors of SQR. Antifungal mechanics: SQR is a novel target for a large family of fungicides, yet the mechanism of action remains unclear, and the bioactive conformation of the inhibitors in the SQR binding pocket has not been identified. In this study, the kinetics of SQR inhibition by ten carboxamide fungicides were measured. Along with results of modeling experiment, these findings provide valuable information for the design of more potent and specific SQR inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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英文
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Comparative Kinetics of Q(1) Site Inhibitors of Cytochrome bc(1) Complex: Picomolar Antimycin and Micromolar Cyazofamid
作者：
Li, Hui;Zhu, Xiao-Lei;Yang, Wen-Chao;Yang, Guang-Fu
* （ 期刊：
CHEMICAL BIOLOGY & DRUG DESIGN ,2014年83(1):71-80 ISSN：1747-0277
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Yang, Wen-Chao; Li, Hui] Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
Cytochrome bc1 complex;antimycin;cyazofamid;enzyme inhibitor;succinate-cytochrome c reductase
摘要：
Antimycin and cyazofamid are specific inhibitors of the mitochondrial respiratory chain and bind to the Qi site of the cytochrome bc 1 complex. With the aim to understand the detailed molecular inhibition mechanism of Qi inhibitors, we performed a comparative investigation of the inhibitory kinetics of them against the porcine bc 1 complex. The results showed that antimycin is a slow tight-binding inhibitor of succinate-cytochrome c reductase (SCR) with Ki = 0.033 ± 0.00027 nm and non-competitive inhibition with respect to cytochrome c. Cyazofamid is a classical inhibitor of SCR with Ki = 12.90 ± 0.91 μm and a non-competitive inhibitor with respect to cytochrome c. Both of them show competitive inhibition with respect to substrate DBH2. Further molecular docking and quantum mechanics calculations were performed. The results showed that antimycin underwent significant conformational change upon the binding. The energy barrier between the conformations in the crystal and in the binding pocket is ~13.63 kcal/mol. Antimycin formed an H-bond with Asp228 and two water-bridged H-bonds with Lys227 and His201, whereas cyazofamid formed only one H-bond with Asp228. The conformational change and the different hydrogen bonding network might account for why antimycin is a slow tight-binding inhibitor, whereas cyazofamid is a classic inhibitor. In this paper, a comparative investigation of the inhibitory kinetics of antimycin and cyazofamid against the porcine bc1 complex was performed. The resulsts show that antimycin was a slow tight-binding inhibitor and cyazofamid was a typical classical inhibitor. Combined with molecular docking and quantum mechanics calculations, the detailed mechanism of inhibition by Qi inhibitors was obtained. © 2013 John Wiley & Sons A/S.
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英文
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Syntheses of coumarin–tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase
作者：
Sun, Qi;Peng, Da-Yong;Yang, Sheng-Gang;Zhu, Xiao-Lei;Yang, Wen-Chao* ;...
期刊：
Bioorganic & Medicinal Chemistry ,2014年22(17):4784-4791 ISSN：0968-0896
通讯作者：
Yang, Wen-Chao
作者机构：
[Yang, Guang-Fu; Yang, Sheng-Gang; Zhu, Xiao-Lei; Yang, Wen-Chao; Sun, Qi; Peng, Da-Yong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构：
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
Acetylcholinesterase inhibitor;Alzheimer's disease;Butylcholinesterase inhibitor;Coumarin
摘要：
Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki = 16.7 nM) against human AChE and about 2-fold lower potency (Ki = 16.1 nM) against BChE than tacrine (Ki = 35.7 nM for AChE, Ki = 8.7 nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aβ aggregation and β-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery. © 2014 Elsevier Ltd. All rights reserved.
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英文
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Structural basis of femtomolar inhibitors for acetylcholinesterase subtype selectivity: Insights from computational simulations
作者：
Zhu, Xiao-Lei;Yu, Ning-Xi;Hao, Ge-Fei;Yang, Wen-Chao;Yang, Guang-Fu
* （ 期刊：
Journal of Molecular Graphics and Modelling ,2013年41:55-60 ISSN：1093-3263
通讯作者：
Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhu, Xiao-Lei; Yang, Wen-Chao; Yu, Ning-Xi; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Cent China Normal Univ, Coll Chem, Luoyu Rd 152, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Luoyu Rd 152, Wuhan 430079, Peoples R China.
关键词：
Acetylcholinesterase;Selectivity;Molecular dynamics;MM/PBSA pi-pi interaction
摘要：
Acetylcholinesterase (AChE) is a key enzyme of the cholinergic nervous system. More than one gene encodes the synaptic AChE target. As the most potent known AChE inhibitor, the syn1-TZ2PA6 isomer was recently shown to have higher affinity as a reversible organic inhibitor of acetylcholinesterase1 (AChE1) than the anti1-TZ2PA6 isomer. Opposite selectivity has been shown for acetylcholinesterase2 (AChE2). In an attempt to understand the selectivity of the syn1-TZ2PA6 and anti1-TZ2PA6 isomers for AChE1 and AChE2, six molecular dynamics (MD) simulations were carried out with mouse AChE (mAChE, type of AChE1), Torpedo californica AChE (TcAChE, type of AChE1), and Drosophila melanogaster AChE (DmAChE, type of AChE2) bound with syn1-TZ2PA6 and anti1-TZ2PA6 isomers. Within the structure of the inhibitor, the 3,8-diamino-6-phenylphenanthridinium subunit and 9-amino-1,2,3,4- tetrahydroacridine subunit, via π-πinteractions, made more favorable contributions to syn1-TZ2PA6 or anti1-TZ2PA6 isomer binding in the mAChE/TcAChE enzyme than the 1,2,3-triazole subunit. Compared to AChE1, the triazole subunit had increased binding energy with AChE2 due to a greater negative charge in the active site. The binding free energy calculated using the MM/PBSA method suggests that selectivity between AChE1 and AChE2 is mainly attributed to decreased binding affinity for the inhibitor. ©2013 Elsevier Inc. All rights reserved.
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英文
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InBr3-Mediated One-Pot Synthesis of 2-(Polyhydroxylatedalkyl)-N-aryl-/-alkylpyrroles from 1,2-Cyclopropa-3pyranone and Amines
作者：
Wang, Pingyuan;Song, Shanshan;Miao, Zehong;Yang, Guangfu
* （ ;Zhang, Ao
期刊：
Organic Letters ,2013年15(15):3852-3855 ISSN：1523-7060
通讯作者：
Yang, Guangfu
作者机构：
[Yang, Guangfu; Wang, Pingyuan] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.;[Wang, Pingyuan; Zhang, Ao] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China.;[Wang, Pingyuan; Zhang, Ao] Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Shanghai 200031, Peoples R China.;[Miao, Zehong; Song, Shanshan] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China.
通讯机构：
[Yang, Guangfu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.
摘要：
An efficient one-pot synthesis of polyhydroxyalkyl-substituted pyrroles from 1,2-cyclopropa-3-pyranones with primary amines is reported. With 10% of InBr3 as the catalyst, both aryl- and alkylamines as well as various 1,2-cyclopropa-3-pyranones are well tolerated. This method is highly appealing because of its one-pot process, mild reaction conditions, substrate simplicity, and broad substrate scope.
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英文
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Synthesis and antifungal activity of 3-(1,3,4-oxadiazol-5-yl)-indoles and 3-(1,3,4-oxadiazol-5-yl)methyl-indoles
作者：
Zhang, Ming-Zhi;Mulholland, Nick;Beattie, David;Irwin, Dianne;Gu, Yu-Cheng;...
期刊：
European Journal of Medicinal Chemistry ,2013年63:22-32 ISSN：0223-5234
通讯作者：
Chen, Qiong
作者机构：
[Yang, Guang-Fu; Zhang, Ming-Zhi; Chen, Qiong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Irwin, Dianne; Clough, John; Gu, Yu-Cheng; Mulholland, Nick; Beattie, David] Syngenta Jealotts Hill Int Res Ctr, Bracknell RG42 6EY, Berks, England.
通讯机构：
[Chen, Qiong] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词：
1,3,4-Oxadiazole;Antifungal activity;Indole;Structure-activity relationships;Synthesis
摘要：
On the basis of the principle of combination of active structural moieties, a modified and efficient synthetic method for three series of novel indole-based 1,3,4-oxadiazoles is described. Bioassays conducted at Syngenta showed that several of the synthesized compounds exhibit higher antifungal activity than pimprinine, the natural product which inspired this synthesis. Two main structural alterations were found to broaden the spectrum of biological activity in most cases. Compounds 3g, 6c, 6e, 6h, 9d, 9e, 9h and 9m (Fig. 1) were identified as the most active on the biological assays, and will be studied further. © 2013 Elsevier Masson SAS. All rights reserved.
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