Synthesis and Bioactivity of Novel Inhibitors for Type III Secretion System of Pseudomonas aeruginosa PAO1

doi:10.6023/cjoc201302021

Chin. J. Org. Chem. ›› 2013, Vol. 33 ›› Issue (06): 1309-1318.DOI: 10.6023/cjoc201302021 Previous Articles Next Articles

Articles

铜绿假单胞菌PAO1III型分泌系统新型抑制剂的合成和生物活性研究

张成芳^a, 吴小刚^b, 李燕^c, 梁翠荣^a, 车亦舟^b, 顾玲玲^a, 任杰^a, 胡昆^a, 孙小强^d, Ching-Hong Yang^b, 陈新^a

a 常州大学制药与生命科学学院常州 213164;
b Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53211, USA;
c 中国农业大学植物病理系北京 100193;
d 常州大学石油化工学院常州 213164

收稿日期:2013-02-26 修回日期:2013-04-01 发布日期:2013-04-08
通讯作者: 陈新, Ching-Hong Yang E-mail:xinchen@cczu.edu.cn;chyang@uwm.edu
基金资助:
国家自然科学基金(No.21272029)和江苏省“333高层次人才培养工程”资助项目.

Synthesis and Bioactivity of Novel Inhibitors for Type III Secretion System of Pseudomonas aeruginosa PAO1

Zhang Chengfang^a, Wu Xiaogang^b, Li Yan^c, Liang Cuirong^a, Che Yizhou^b, Gu Lingling^a, Ren Jie^a, Hu Kun^a, Sun Xiaoqiang^d, Yang Ching-Hong^b, Chen Xin^a

a School of Pharmaceutical and Life Science, Changzhou University, Changzhou 213164;
b Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53211, USA;
c Department of Plant Disease, China Agricultural University, Beijing 100193;
d School of Petrochemical Engineering, Changzhou University, Changzhou 213164

Received:2013-02-26 Revised:2013-04-01 Published:2013-04-08
Supported by:
Project supported by the National Natural Science Foundation of China (No.21272029) and the "333 High-level talent training program" of Jiangsu Province.

Pseudomonas aeruginosa PAO1 is a Gram-negative, opportunistic bacterial human pathogen which infects immunocompromised individuals.The bacterium carries a type III secretion system (T3SS) as a major virulence determinant.The strategy of T3SS inhibitors is to prevent the bacterium from injecting effector proteins into the host, and causing a change in the pathophysiology of the host cells.Based on the structure of a known T3SS inhibitor of P.aeruginosa, 20 new α-phenoxyacetamide derivatives have been designed and synthesized, and the structure-activity relationship results for these new derivatives have been discussed.Five derivatives have shown strong inhibitory effect against exoS gene expression of P.aeruginosa, and among them, N-(2-pyridylmethyl)-2-(2,4-dichlorophenoxy)-butanamide (5r) has not only exhibited stronger potency than the known T3SS inhibitor, but also better solubility in aqueous solution.

Key words: Pseudomonas aeruginosa, type III secretion system, inhibitors, synthesis

Cite this article

Zhang Chengfang, Wu Xiaogang, Li Yan, Liang Cuirong, Che Yizhou, Gu Lingling, Ren Jie, Hu Kun, Sun Xiaoqiang, Yang Ching-Hong, Chen Xin. Synthesis and Bioactivity of Novel Inhibitors for Type III Secretion System of Pseudomonas aeruginosa PAO1[J]. Chin. J. Org. Chem., 2013, 33(06): 1309-1318.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Gould, I.M.Int. J. Antimicrob. Agents 2009, 34(Suppl.3), S2.
[2] Keyser, P.; Elofsson, M.; Rosell, S.; Wolf-Watz, H.J.Intern.Med. 2008, 264, 17.
[3] Ghosh, P.Microbiol.Mol.Biol.Rev.2004, 68, 771.
[4] Engel, J.; Balachandran, P.Curr.Opin.Microbiol.2009, 12, 61.
[5] Izore, T.; Job, V.; Dessen, A. Structure 2011, 19, 603.
[6] Hung, D.T.; Shakhnovich, E.A.; Pierson, E.; Mekalanos, J.J.Science 2005, 310, 670.
[7] Muschiol, S.; Bailey, L.; Gylfe, A.; Sundin, C.; Hultenby, K.; Bergstom, S.; Elofsson, M.; Wolf-Wate, H.; Normark, S.; Henriques-Normark, B.Proc.Natl.Acad.Sci.U.S.A.2006, 103, 14566.
[8] Hudson, D.L.; Layton, A.N.; Field, T.R.; Bowen, A.J.; Wolf-Watz, H.; Elofsson, M.; Stevens, M.P.; Galyov, E.E.An.Agents Chemother. 2007, 51, 2631.
[9] Poole, K.Clin.Microbiol.Infect. 2004, 10, 12.
[10] Hauser, A.R.Nat.Rev.Microbiol.2009, 7, 654.
[11] Engel, J.; Balachandran, P.Curr.Opin.Microbiol. 2009, 12, 61.
[12] Aiello, A.; Williams, J.D.; Majgier-Baranowska, H.; Patel, I.; Peet, N.P.; Huang, J.; Lory, S.; Bowlin, T.L.; Moir, D.T.Antimicrob. Agents Chemother.2010, 54, 1988.
[13] Pu, Y.J.; Vaid, R.K.; Boini, S.K.; Towsley, R.W.; Doecke, C.W.; Mitchell, D.Org.Proc.Res.Dev.2009, 13, 310.
[14] Moir, D.T.; Aiello, D.; Peet, N.P.; Williams, J.D.; Torham, M.WO 2013010089, 2013[Chem.Abstr.2013, 158, 205450].
[15] Grabouska, E.; Arct, J.; Eckstein, Z.Rocz.Chem.1969, 43, 715.
[16] Winternitz, P.DE 2635327, 1977[Chem.Abstr.1977, 87, 67967].
[17] Akhtar, T.; Hameed, S.; Al-Masoudi, N.A.; Loddo, R.; La Colla, P.Acta Pharm. 2008, 58, 135.
[18] Duintijer, E.; Jonsson, A.Acta Chem.Scand. 1954, 8, 1493.
[19] Tarasiuk, B.Chemia 2006, 61, 171.
[20] Rao, V.R.; Reddy, G.V.; Yadla, R.; Narsaiah, B.; Rao, P.S.ARKIVOC 2005, 3, 211.
[21] Hayashi, K.; Tan, X.; Zheng, N.; Hatate, T.; Kimura, Y.; Kepinski, S.; Nozaki, H.Proc.Natl.Acad.Sci.U.S.A.2008, 105, 5632.
[22] Moir, D.T.; Aiello, D.; Peet, N.P.; Williams, J.D.; Torham, M.WO 2013010082, 2013[Chem.Abstr.2013, 158, 205446].
[23] Yamazaki, A.; Li, J.; Zeng, Q.; Khokhani, D.; Hutchins, W.; Yost, A.; Biddle, E.; Toone, E T.; Chen, X.; Yang, C.H.Antimiciob.Agents Chemother. 2012, 56, 36.

铜绿假单胞菌PAO1III型分泌系统新型抑制剂的合成和生物活性研究

Synthesis and Bioactivity of Novel Inhibitors for Type III Secretion System of Pseudomonas aeruginosa PAO1

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[2]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[3]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[4]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[5]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[6]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[7]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[8]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[9]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[10]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[11]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[12]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[13]	Yang Li, Jinding Yuan, Di Zhao. Deep Eutectic Solvent of 1,3-Dimethylurea/L-(+)-Tartaric Acid for the Green Synthesis of (E)-2-Styrylquinoline-3-carboxylic Acid Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3268-3276.
[14]	Dandan Sui, Nannan Cen, Ruoqu Gong, Yang Chen, Wenbo Chen. Supporting-Electrolyte-Free Electrochemical Synthesis of Trifluoromethylated Oxindoles in Continuous Flow [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3239-3245.
[15]	Huanqing Li, Zhaohua Chen, Zujia Chen, Qiwen Qiu, Youcai Zhang, Sihong Chen, Zhaoyang Wang. Research Progress in Mercury Ion Fluorescence Probes Based on Organic Small Molecules [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3067-3077.