An Activity-Based Fluorogenic Probe Enables Cellular and in Vivo Profiling of Carboxylesterase Isozymes
作者:
Liu, Shi-Yu;Qu, Ren-Yu;Li, Rong-Rong;Yan, Yao-Chao;Sun, Yao;...
期刊:
Analytical Chemistry ,2020年92(13):9205-9213 ISSN:0003-2700
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
( 杨光富 )
作者机构:
[Yang, Guang-Fu; Liu, Shi-Yu; Li, Rong-Rong; Yang, Wen-Chao; Qu, Ren-Yu; Yan, Yao-Chao; Sun, Yao; Yang, WC; Yang, GF] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ,Int Joint Res Ctr Intelligent Biosens, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Liu, Shi-Yu; Li, Rong-Rong; Yang, Wen-Chao; Qu, Ren-Yu; Yan, Yao-Chao; Sun, Yao; Yang, WC; Yang, GF] Cent China Normal Univ, Coll Chem, Chem Biol Ctr, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构:
[Yang, Guang-Fu; Yang, WC; Yang, GF] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ,Int Joint Res Ctr Intelligent Biosens, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Coll Chem, Chem Biol Ctr, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
摘要:
Carboxylesterases (CEs) exist as multiple types of isomers in humans, and two major types are CE1 and CE2. They are widely distributed in human tissues and well-known for their important roles in drug metabolism and pathology of various diseases. Thus, the detection of CEs in living systems could provide efficient proof in disease diagnostics, as well as important information regarding chemotherapeutic effects of antitumor drugs and prognosis. To develop a specific probe to discriminate CEs from other hydrolases, especially cholinesterases, is quite challenging due to their structural similarities and substrate specificity. To date, almost all of the fluorescent probes developed for CEs have been constructed with an acetyl group as the recognition unit. Herein we proposed a new design strategy of probe-cavity matching, which led to the identification of a new fluorogenic substrate (termed as HBT-CE) with high specificity toward both CE isomers and improved sensitivity, considering the higher binding affinity and catalysis efficiency. The promising capability of HBT-CE was further demonstrated for endogenous CEs imaging in living cells, zebrafish, and nude mice. In addition, HBT-CE was successfully applied in kinetically monitoring drug-induced CE regulation in cancer cells. All of these findings suggest that HBT-CE is a valuable tool for tracking and imaging endogenous CEs in complex biological systems. Copyright © 2020 American Chemical Society.
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英文
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Activity-based near-infrared fluorogenic probe for enabling in vitro and in vivo profiling of neutrophil elastase
作者:
Liu, Shi-Yu;Xiong, Hao;Li, Rong-Rong;Yang, Wen-Chao
* ;Yang, Guang-Fu
* ( 杨光富 )
期刊:
Analytical Chemistry ,2019年91(6):3877-3884 ISSN:0003-2700
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
( 杨光富 )
作者机构:
[Yang, Guang-Fu; Liu, Shi-Yu; Li, Rong-Rong; Xiong, Hao; Yang, Wen-Chao; Yang, WC; Yang, GF] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;[Yang, Guang-Fu; Liu, Shi-Yu; Li, Rong-Rong; Xiong, Hao; Yang, Wen-Chao; Yang, WC; Yang, GF] Cent China Normal Univ, Coll Chem, Chem Biol Ctr, 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, Guang-Fu; Yang, WC; Yang, GF] C;Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;Cent China Normal Univ, Coll Chem, Chem Biol Ctr, Wuhan 430079, Hubei, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
摘要:
Neutrophil elastase (NE), a typical hematopoietic serine protease, has significant roles in inflammatory and immune responses, and thus is highly associated with various diseases such as acute lung injury (ALI) and lung cancer. Rapid and accurate measurement of NE activity in biological systems is particularly important for understanding the role of NE in inflammatory diseases, as well as clinical diagnosis. However, the specific detection and noninvasive imaging of NE in vivo remains a challenge. To address this issue, a small-molecule substrate based near-infrared fluorogenic probe (NEP) for NE was constructed via incorporating pentafluoroethyl as the recognition group with a hemicyanine dye-based fluorophore. This initially quenched probe possesses more than 25-fold red fluorescence enhancement upon the catalysis of human NE, and the detection limit is about 29.6 ng/mL. In addition, the high specificity and the long emission wavelength (Î" em max = 700 nm) of NEP allowed the direct monitoring of NE-trafficking, exogenous NE uptake, and endogenous NE upregulation at the cellular level. Moreover, the successful spatiotemporal imaging of NE in ALI model mice also made it a promising new tool in clinical diagnosis for ALI and other lung diseases. © 2019 American Chemical Society.
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英文
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STRUCTURE-BASED DISCOVERY OF POTENTIAL FUNGICIDES AS SUCCINATE UBIQUINONE OXIDOREDUCTASE INHIBITORS
作者:
Xiong, Li;Li, Hua;Jiang, Li-Na;Ge, Jing-Ming;Yang, Wen-Chao;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2017年65(5):1021-1029 ISSN:0021-8561
通讯作者:
Zhu, Xiao Lei;Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Li, Hua; Xiong, Li; Ge, Jing-Ming; Yang, Wen-Chao; Jiang, Li-Na; Zhu, Xiao Lei; Yang, GF] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
通讯机构:
[Zhu, XL; Yang, GF; Yang, Guang-Fu] C;Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
关键词:
complex II;diphenyl ether;molecular docking;structure-activity relationship;succinate ubiquinone oxidoreductase
摘要:
A series of diphenyl ether-containing pyrazole-carboxamide derivatives was designed and synthesized as new succinate ubiquinone oxidoreductase (SQR) inhibitors. This highly potent molecular scaffold was developed from a moderately activie hit 3, obtained from our previous pharmacophore-linked fragment virtual screening (PFVS) method. The results of greenhouse tests indicated that some analogues showed good SQR inhibitory activity, with promising fungicidal activity against Rhizoctonia solani and Sphaerotheca fuliginea at a dosage of 200 mg/L. Most surprisingly, compound 62 showed the highest SQR inhibitory activity with a K<inf>i</inf>value of 0.081 μM, about 4-fold more potent than penthiopyrad (K<inf>i</inf>= 0.307 μM). In addition, compounds 43 and 62 displayed excellent fungicidal activity even at a dosage as low as 6.25 mg/L, which was superior to thifluzamide. Moreover, compound 62 exhibited excellent protection effect against R. solani and provided about 81.2% protective control efficancy after 21 days with two sprayings. The present work indicated that these two compounds could be used as potential agricultural fungicides targeting SQR. ©2017 American Chemical Society.
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英文
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Discovery of New 2-[(4,6-Dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic Acids as Flexible Inhibitors of Arabidopsis thaliana Acetohydroxyacid Synthase and Its P197L Mutant
作者:
Qu, Ren-Yu;Yang, Jing-Fang;Devendar, Ponnam;Kang, Wei-Ming;Liu, Yu-Chao;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2017年65(51):11170-11178 ISSN:0021-8561
通讯作者:
Yang, Guang-Fu;Xi, Zhen
作者机构:
[Yang, Guang-Fu; Devendar, Ponnam; Kang, Wei-Ming; Liu, Yu-Chao; Qu, Ren-Yu; Chen, Qiong; Yang, Jing-Fang] Cent China Normal Univ CCNU, Minist Educ, Key Lab Pesticide & Chem Biol, Coll Chem, Wuhan 430079, Hubei, Peoples R China.;[Xi, Zhen; Niu, Cong-Wei] Nankai Univ NKU, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;[Yang, Guang-Fu; Xi, Z; Yang, GF; Xi, Zhen] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构:
[Yang, Guang-Fu; Xi, Z; Yang, GF] C;[Xi, Zhen] N;Cent China Normal Univ CCNU, Minist Educ, Key Lab Pesticide & Chem Biol, Coll Chem, Wuhan 430079, Hubei, Peoples R China.;Nankai Univ NKU, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
关键词:
AHAS inhibitors;P197L mutant;antiresistance property;herbicidal activity;molecular docking;structure-activity relationship
摘要:
In the search for new antiresistance acetohydroxyacid synthase (AHAS, EC 2.2.1.6) inhibitors to combat weed resistance associated with AHAS mutations, a series of 2-[(4,6-dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic acids 11-38 were designed and synthesized via the strategy of conformational flexibility analysis. Compounds 21, 22, 26, 33, 36, and 38 with high potency against both wild-type AtAHAS and its P197L mutant were identified as promising candidates with low resistance factors (RF, defined as the ratio between the k<inf>i</inf>values toward P197L mutant and wild-type AHAS) ranging from 0.73 to 6.32. Especially, compound 22 (RF = 0.73) was further identified as the most potent antiresistance AHAS inhibitor because of its significantly reduced resistance level compared with that of tribenuron-methyl (RF = 2650) and bispyribac (RF = 4.57). Furthermore, compounds 26, 33, 36, and 38 also displayed promising herbicidal activities against sensitive and resistant (P197L) Descurainia sophia at the dosage of 75-150 g of active ingredient (ai)/ha. Notably, compounds 33 and 38 still maintained over 60% herbicidal activity toward the resistant weed even at much lower dosages (37.5 g ai/ha). Therefore, the designed scaffold has the great potential to discover new candidate compounds for the control of weed resistance associated with AHAS mutation.<br/> ©2017 American Chemical Society.
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英文
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Synthesis and Herbicidal Activity of Pyrido[2,3-d]pyrimidine-2,4-dione-Benzoxazinone Hybrids as Protoporphyrinogen Oxidase Inhibitors
作者:
Wang, Da-Wei;Li, Qian;Wen, Kai;Ismail, Ismail;Liu, Dan-Dan;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2017年65(26):5278-5286 ISSN:0021-8561
通讯作者:
Xi, Zhen;Yang, Guang-Fu
作者机构:
[Li, Qian; Wen, Kai; Xi, Zhen; Niu, Cong-Wei; Wen, Xin; Liu, Dan-Dan; Wang, Da-Wei; Ismail, Ismail] Nankai Univ, State Key Lab Elementoorgan Chem, Coll Chem, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.;[Li, Qian; Wen, Kai; Xi, Zhen; Niu, Cong-Wei; Wen, Xin; Liu, Dan-Dan; Wang, Da-Wei; Ismail, Ismail] Nankai Univ, Dept Chem Biol, Coll Chem, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.;[Yang, Guang-Fu] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
通讯机构:
[Xi, Zhen] N;[Yang, Guang-Fu] C;Nankai Univ, State Key Lab Elementoorgan Chem, Coll Chem, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.;Nankai Univ, Dept Chem Biol, Coll Chem, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词:
benzoxazinone;herbicide;protoporphyrinogen oxidase;pyrido[2,3-d]pyrimidine-2,4-dione;structure-activity relationship
摘要:
To search for new protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with improved bioactivity, a series of novel pyrido[2,3-d]pyrimidine-2,4-dione-benzoxazinone hybrids, 9-13, were designed and synthesized. Several compounds with improved tobacco PPO (mtPPO)-inhibiting and promising herbicidal activities were found. Among them, the most potent compound, 3-(7-fluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-benzo[b][1,4] oxazin-6-yl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 11q, with a K<inf>i</inf>value of 0.0074 μM, showed six times more activity than flumioxazin (K<inf>i</inf>= 0.046 μM) against mtPPO. Compound 11q displayed a strong and broad spectrum of weed control at 37.5-150 g of active ingredient (ai)/ha by both post- and pre-emergence application, which was comparable to that of flumioxazin. 11q was safe to maize, soybean, peanut, and cotton at 150 g ai/ha, and selective to rice and wheat at 75 g ai/ha by pre-emergence application, indicating potential applicability in these fields. ©2017 American Chemical Society.
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英文
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4-Hydroxyphenylpyruvate dioxygenase inhibitors: From chemical biology to agrochemicals
作者:
Ndikuryayo, Ferdinand;Moosavi, Behrooz;Yang, Wen-Chao
* ;Yang, Guang-Fu
* ( 杨光富 )
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2017年65(39):8523-8537 ISSN:0021-8561
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Ndikuryayo, Ferdinand; Moosavi, Behrooz; Yang, Wen-Chao; Yang, WC; Yang, GF] Cent China Normal Univ, Coll Chem, 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, WC; Yang, GF; Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Hubei, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
关键词:
4-hydroxyphenylpyruvate dioxygenase;agrochemical;chemical biology;herbicide;inhibitor
摘要:
The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an enzyme engaged in photosynthetic activity and catalyzes the transformation of 4-hydroxyphenylpyruvic acid (HPPA) into homogentisic acid (HGA). HPPD inhibitors constitute a promising area of discovery and development of innovative herbicides with some advantages, including excellent crop selectivity, low application rates, and broad-spectrum weed control. HPPD inhibitors have been investigated for agrochemical interests, and some of them have already been commercialized as herbicides. In this review, we mainly focus on the chemical biology of HPPD, discovery of new potential inhibitors, and strategies for engineering transgenic crops resistant to current HPPD-inhibiting herbicides. The conclusion raises some relevant gaps for future research directions.
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英文
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Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach
作者:
Xiong, Li;Zhu, Xiao-Lei
* ;Gao, Hua-Wei;Fu, Yu
( 杨光富 ) ;Hu, Sheng-Quan;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2016年64(24):4830-4837 ISSN:0021-8561
通讯作者:
Zhu, Xiao-Lei;Yang, Guang-Fu
作者机构:
[Fu, Yu; Hu, Sheng-Quan; Zhu, Xiao-Lei; Xiong, Li; Yang, Wen-Chao; Gao, Hua-Wei; Jiang, Li-Na] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Fu, Yu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.;[Zhu, XL; Yang, GF] Ctr China Normal Univ, Luoyu Rd 152, Wuhan 43007, Peoples R China.
通讯机构:
[Zhu, XL; Yang, GF] C;Ctr China Normal Univ, Luoyu Rd 152, Wuhan 43007, Peoples R China.
关键词:
succinate-ubiquinone oxidoreductase;complex II;pharmacophore-linked fragment virtual screening;molecular modeling;structure-based design
摘要:
Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a K<inf>i</inf>value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R<sup>2</sup>group had a significant effect on binding with the protein. ©2016 American Chemical Society.
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英文
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Recent advances in cytokine detection by immunosensing
作者:
Liu, Guozhen
* ;Qi, Meng;Hutchinson, Mark R.;Yang, Guangfu
( 杨光富 ) ;Goldys, Ewa M.
*
期刊:
Biosensors and Bioelectronics ,2016年79:810-821 ISSN:0956-5663
通讯作者:
Liu, Guozhen;Goldys, Ewa M.
作者机构:
[Yang, Guangfu; Liu, Guozhen; Qi, Meng] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Goldys, Ewa M.; Liu, Guozhen] Macquarie Univ, ARC Ctr Excellence Nanoscale Biophoton CNBP, N Ryde, NSW 2109, Australia.;[Hutchinson, Mark R.] Univ Adelaide, ARC Ctr Excellence Nanoscale Biophoton CNBP, Adelaide, SA 5005, Australia.
通讯机构:
[Liu, Guozhen] C;[Goldys, Ewa M.] M;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Macquarie Univ, ARC Ctr Excellence Nanoscale Biophoton CNBP, N Ryde, NSW 2109, Australia.
关键词:
Cytokines;Immunosensing;Microfluidics;Real-time detection;Review;Sensitivity
摘要:
The detection of cytokines in body fluids, cells, tissues and organisms continues to attract considerable attention due to the importance of these key cell signaling molecules in biology and medicine. In this review, we describe recent advances in cytokine detection in the course of ongoing pursuit of new analytical approaches for these trace analytes with specific focus on immunosensing. We discuss recent elegant designs of sensing interface with improved performance with respect to sensitivity, selectivity, stability, simplicity, and the absence of sample matrix effects. Various immunosensing approaches based on multifunctional nanomaterials open novel opportunities for ultrasensitive detection of cytokines in body fluids in vitro and in vivo. Methodologies such as suspension arrays also known as bead assays together with optical fiber-based sensors, on their own or in combination with microfluidic devices will continue to have an important role to address the grand challenge of real-time in vivo multiplex cytokine detection. © 2016 Elsevier B.V.
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英文
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Detection of Intracellular Selenol-Containing Molecules Using a Fluorescent Probe with Near-Zero Background Signal
作者:
Sun, Qi;Yang, Shu-Hou;Wu, Lei;Dong, Qing-Jian;Yang, Wen-Chao* ;...
期刊:
Analytical Chemistry ,2016年88(11):6084-6091 ISSN:0003-2700
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Yang, Wen-Chao; Sun, Qi; Yang, Shu-Hou; Wu, Lei; Yang, WC; Yang, GF] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Dong, Qing-Jian] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Nucl Med, Tongji Med Coll, Wuhan 430030, Peoples R China.
通讯机构:
[Yang, WC; Yang, GF] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
摘要:
Selenocysteine (Sec), encoded as the 21st amino acid, is the predominant chemical form of selenium that is closely related to various human diseases. Thus, it is of high importance to identify novel probes for sensitive and selective recognition of Sec and Sec-containing proteins. Although a few probes have been reported to detect artificially introduced selenols in cells or tissues, none of them has been shown to be sensitive enough to detect endogenous selenols. We report the characterization and application of a new fluorogenic molecular probe for the detection of intracellular selenols. This probe exhibits near-zero background fluorescence but produces remarkable fluorescence enhancement upon reacting with selenols in a fast chemical reaction. It is highly specific and sensitive for intracellular selenium-containing molecules such as Sec and selenoproteins. When combined with flow cytometry, this probe is able to detect endogenous selenols in various human cancer cells. It is also able to image endogenous selenol-containing molecules in zebrafish under a fluorescence microscope. These results demonstrate that this molecular probe can function as a useful molecular tool for intracellular selenol sensing, which is valuable in the clinical diagnosis for human diseases associated with Sec-deficiency or overdose. © 2016 American Chemical Society.
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英文
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Synthesis, Herbicidal Activity, and QSAR of Novel N-Benzothiazolyl-pyrimidine-2,4-diones as Protoporphyrinogen Oxidase Inhibitors
作者:
Zuo, Yang;Wu, Qiongyou;Su, Sun-Wen;Niu, Cong-Wei;Xi, Zhen;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2016年64(3):552-562 ISSN:0021-8561
通讯作者:
Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Su, Sun-Wen; Zuo, Yang; Wu, Qiongyou] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Niu, Cong-Wei; Xi, Zhen] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
通讯机构:
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词:
benzothiazole;herbicide;molecular design;protoporphyrinogen oxidase;pyrimidinedione
摘要:
Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is known as a key action target for several structurally diverse herbicides. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel 3-(2′-halo-5′-substituted-benzothiazol-1′-yl)-1-methyl-6-(trifluoromethyl)pyrimidine-2,4-diones 9 were designed and synthesized. The bioassay results indicated that a number of the newly synthesized compounds exhibited higher inhibition activity against tobacco PPO (mtPPO) than the controls, saflufenacil and sulfentrazone. Compound 9F-5 was identified as the most potent inhibitor with a K<inf>i</inf>value of 0.0072 ΜM against mtPPO, showing about 4.2-fold and 1.4-fold higher potency than sulfentrazone (K<inf>i</inf>= 0.03 ΜM) and saflufenacil (K<inf>i</inf>= 0.01 ΜM), respectively. An additional green house assay demonstrated that compound 9F-6 (K<inf>i</inf>= 0.012 ΜM) displayed the most promising postemergence herbicidal activity with a broad spectrum even at a concentration as low as 37.5 g of active ingredient (ai)/ha. Maize exhibits relative tolerance against compound 9F-6 at the dosage of 150 g ai/ha, but it is susceptible to saflufenacil even at 75 g ai/ha. Thus, compound 9F-6 exhibits the potential to be a new herbicide for weed control in maize fields. ©2016 American Chemical Society.
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英文
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Discovery of cytochrome bc1 complex inhibitors inspired by the natural product karrikinolide
作者:
Chen, Cheng;Wu, Qiong-You* ;Shan, Lian-Ying;Zhang, Bei;Verpoort, Francis;...
期刊:
RSC Advances ,2016年6(100):97580-97586 ISSN:2046-2069
通讯作者:
Wu, Qiong-You;Yang, Guang-Fu
作者机构:
[Chen, Cheng; Verpoort, Francis] Wuhan Univ Technol, State Key Lab Adv Technol Mat Synth & Proc, Wuhan 430070, Peoples R China.;[Yang, Guang-Fu; Shan, Lian-Ying; Wu, Qiong-You; Yang, GF; Zhang, Bei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
通讯机构:
[Wu, QY; Yang, GF] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要:
The cytochrome bc<inf>1</inf>complex (cyt bc<inf>1</inf>or complex III) is a promising target of numerous antibiotics and fungicides. With an aim to indentify new lead structures for the bc<inf>1</inf>complex, a series of novel inhibitors were discovered from the natural product karrikinolide for the first time. Extensive screening results suggested variable inhibitory activities of these compounds against succinate-cytochrome reductase [SCR, a mixture of respiratory complex II (SQR) and complex III (the bc<inf>1</inf>complex)], implying the essential role of a 4-substituted phenyl group for the high potency. Exceptionally, compound 12g showed excellent inhibition potency having an IC<inf>50</inf>value in the sub-micromolar range, demonstrating its higher potency than the commercial control amisulbrom by over two orders of magnitude. Further experiments inferred that these newly prepared compounds mainly target the bc<inf>1</inf>complex. Seemingly, this work has presented a new lead scaffold for further development of bc<inf>1</inf>complex inhibitors.<br/> ©2016 The Royal Society of Chemistry.
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英文
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An Efficient One-Pot Synthesis of 2-(Aryloxyacetyl)cyclohexane-1,3-diones as Herbicidal 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
作者:
Wang, Da-Wei;Lin, Hong-Yan;He, Bo;Wu, Feng-Xu;Chen, Tao;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2016年64(47):8986-8993 ISSN:0021-8561
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Yang, Wen-Chao; Chen, Tao; Chen, Qiong; Wang, Da-Wei; Lin, Hong-Yan; Wu, Feng-Xu; He, Bo; Yang, WC; Yang, GF] 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, WC; Yang, GF; Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
关键词:
*4-hydroxyphenylpyruvate dioxygenase;*herbicidal activity;*one-pot synthesis;*structure-activity relationship;*triketone
摘要:
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is an important target for new bleaching herbicides discovery. As a continuous work to discover novel crop selective HPPD inhibitor, a series of 2-(aryloxyacetyl)cyclohexane-1,3-diones were rationally designed and synthesized by an efficient one-pot procedure using N,N′-carbonyldiimidazole (CDI), triethylamine, and acetone cyanohydrin in CH<inf>2</inf>Cl<inf>2</inf>. A total of 58 triketone compounds were synthesized in good to excellent yields. Some of the triketones displayed potent in vitro Arabidopsis thaliana HPPD (AtHPPD) inhibitory activity. 2-(2-((1-Bromonaphthalen-2-yl)oxy)acetyl)-3-hydroxycyclohex-2-en-1-one, II-13, displayed high, broad-spectrum, and postemergent herbicidal activity at the dosage of 37.5-150 g ai/ha, nearly as potent as mesotrione against some weeds. Furthermore, II-13 showed good crop safety against maize and canola at the rate of 150 g ai/ha, indicating that II-13 might have potential as a herbicide for weed control in maize and canola fields. II-13 is the first HPPD inhibitor showing good crop safety toward canola. ©2016 American Chemical Society.
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英文
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Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation
作者:
Liu, Yu-Chao;Qu, Ren-Yu;Chen, Qiong;Yang, Jing-Fang;Cong-Wei, Niu;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2016年64(24):4845-4857 ISSN:0021-8561
通讯作者:
Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Yang, Jing-Fang; Liu, Yu-Chao; Chen, Qiong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Zhen, Xi; Cong-Wei, Niu] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;[Yang, Guang-Fu; Zhen, Xi] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构:
[Yang, Guang-Fu] C;[Yang, Guang-Fu] N;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
关键词:
molecular design;herbicide;weed resistance;acetohydroxyacid synthase;triazolopyrimidines
摘要:
Acetohydroxyacid synthase (AHAS;also known as acetolactate synthase;EC 2.2.1.6, formerly EC 4.1.3.18) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. Weed resistance to AHAS-inhibiting herbicides, increasing at an exponential rate, is becoming a global problem and leading to an urgent demand of developing novel compounds against both resistant and wild AHAS. In the present work, a series of novel 2-aroxyl-1,2,4-triazolopyrimidine derivatives (a total of 55) were designed and synthesized with the aim to discover an antiresistant lead compound. Fortunately, the screening results indicated that many of the newly synthesized compounds showed a better, even excellent, inhibition effect against both the wild-type Arabidopsis thaliana AHAS and P197L mutants. Among them, compounds 5-3 to 5-17, compounds 5-19 to 5-26, compounds 5-28 to 5-45, and compound 5-48 have the lower values of resistance factor (RF) and display a potential power to overcome resistance associated with the P197L mutation in the enzyme levels. Further greenhouse in vivo assay showed that compounds 5-15 and 5-20 displayed "moderate" to "good" herbicidal activity against both the wild type-and the resistant (P197L mutation) Descurainia sophia, even at a rate as low as 0.9375 (g of ai/ha). The above results indicated that these two compounds could be used as new leads for the future development of antiresistance herbicides. ©2016 American Chemical Society.
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英文
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A Highly Sensitive and Selective Fluorescent Probe for Thiophenol Designed via a Twist-Blockage Strategy
作者:
Sun, Qi;Yang, Shu-Hou;Wu, Lei;Yang, Wen-Chao
* ;Yang, Guang-Fu
* ( 杨光富 )
期刊:
Analytical Chemistry ,2016年88(4):2266-2272 ISSN:0003-2700
通讯作者:
Yang, Wen-Chao;Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Yang, Wen-Chao; Sun, Qi; Yang, Shu-Hou; Wu, Lei; Yang, WC; Yang, GF] 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, WC; Yang, GF; Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
摘要:
A benzoquinolizine coumarin-based fluorescent probe was developed for detecting thiophenols, demonstrating the superior fluorescence properties caused by the decay of the twisting effect of N,N-diethylamino group of coumarin. It discriminated thiophenols from various analytes including aliphatic thiols with good selectivity and displayed ∼700-fold fluorescence intensity enhancement and a remarkable limit of detection (4.5 nM). The new probe also can be applied to quantitative determine the concentrations of thiophenol in water samples and living cells. © 2016 American Chemical Society.
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英文
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Synthesis and Herbicidal Activity of Triketone-Quinoline Hybrids as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
作者:
Wang, Da-Wei;Lin, Hong-Yan;Cao, Run-Jie;Chen, Tao;Wu, Feng-Xu;...
期刊:
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ,2015年63(23):5587-5596 ISSN:0021-8561
通讯作者:
Chen, Qiong
作者机构:
[Yang, Guang-Fu; Yang, Wen-Chao; Chen, Tao; Chen, Qiong; Wang, Da-Wei; Lin, Hong-Yan; Wu, Feng-Xu; Cao, Run-Jie; Hao, Ge-Fei] 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:
4-hydroxyphenylpyruvate dioxygenase;herbicide;quinoline;triketone;rational design
摘要:
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most important targets for herbicide discovery. In the search for new HPPD inhibitors with novel scaffolds, triketone-quinoline hybrids were designed and subsequently optimized on the basis of the structure-activity relationship (SAR) studies. Most of the synthesized compounds displayed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD), and some of them exhibited broad-spectrum and promising herbicidal activity at the rate of 150 g ai/ha by postemergence application. Most promisingly, compound III-l, 3-hydroxy-2-(2-methoxy-7-(methylthio)quinoline-3-carbonyl)cyclohex-2-enone (K<inf>i</inf>= 0.009 ∼M, AtHPPD), had broader spectrum of weed control than mesotrione. Furthermore, compound III-l was much safer to maize at the rate of 150 g ai/ha than mesotrione, demonstrating its great potential as herbicide for weed control in maize fields. Therefore, triketone-quinoline hybrids may serve as new lead structures for novel herbicide discovery. ©2015 American Chemical Society.
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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
( 杨光富 ) ;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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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
* ( 杨光富 )
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.
语种:
英文
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An efficient one-pot access to N-(pyridin-2-ylmethyl) substituent biphenyl-4-sulfonamides through water-promoted, palladium-catalyzed, microwave-assisted reactions
作者:
Huang, Zhi-You;Yang, Jing-Fang;Chen, Qian;Cao, Run-Jie;Huang, Wei;...
期刊:
RSC Advances ,2015年5(92):75182-75186 ISSN:2046-2069
通讯作者:
Yang, Guang-Fu
作者机构:
[Yang, Guang-Fu; Yang, Jing-Fang; Huang, Wei; Huang, Zhi-You; Chen, Qian; Cao, Run-Jie; Hao, Ge-Fei] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.
通讯机构:
[Yang, Guang-Fu] C;Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要:
An efficient one-pot, Pd(PPh<inf>3</inf>)<inf>4</inf>catalyzed, water-promoted method for the synthesis of N-(pyridin-2-ylmethyl) biphenyl-4-sulfonamides was developed under microwave irradiation. This methodology is acid free, has good substrate scope, excellent functional group compatibility, and excellent product yields, and is superior to the existing procedures for the synthesis of biphenyl-4-sulfonamides bearing a pyridin-2-ylmethyl group. ©The Royal Society of Chemistry.
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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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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.
语种:
英文
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