Dihydropyrrolones as bacterial quorum sensing inhibitors

被引：28

作者：

Almohaywi, Basmah ^{[1
,2
]}

Yu, Tsz Tin ^{[1
]}

Iskander, George ^{[1
]}

Chan, Daniel S. H. ^{[1
]}

Ho, Kitty K. K. ^{[1
]}

Rice, Scott ^{[3
]}

Black, David StC ^{[1
]}

Griffith, Renate ^{[4
]}

Kumar, Naresh ^{[1
]}

机构：

[1] UNSW Sydney, Sch Chem, Sydney, NSW 2052, Australia

[2] King Khalid Univ Abha, Sch Pharm, Abha 62529, Saudi Arabia

[3] Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore 639798, Singapore

[4] UNSW Sydney, Dept Pharmacol, Sch Med Sci, Sydney, NSW 2052, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 09期

基金：

澳大利亚研究理事会;

关键词：

Quorum sensing; Biofilm inhibition; Dihydropyrrolone; P; aeruginosa; PSEUDOMONAS-AERUGINOSA;

D O I：

10.1016/j.bmcl.2019.03.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bacteria regulate their pathogenicity and biofilm formation through quorum sensing (QS), which is an intercellular communication system mediated by the binding of signaling molecules to QS receptors such as LasR. In this study, a range of dihydropyrrolone (DHP) analogues were synthesized via the lactone-lactam conversion of lactone intermediates. The synthesized compounds were tested for their ability to inhibit QS, biofilm formation and bacterial growth of Pseudomonas aeruginosa. The compounds were also docked into a LasR crystal structure to rationalize the observed structure-activity relationships. The most active compound identified in this study was compound 9i, which showed 63.1% QS inhibition of at 31.25 mu M and 60% biofilm reduction at 250 mu M with only moderate toxicity towards bacterial cell growth.

引用

页码：1054 / 1059

页数：6

共 22 条

[1] Synthesis of 4-substituted 1,5-dihydropyrrol-2-ones and 5,6-dihydro-1H-pyridin-2-ones by Negishi cross-coupling reactions:: Short access to the antidepressant (±)-rolipram [J].

Albrecht, Dominik ;

Bach, Thorsten .

SYNLETT, 2007, (10) :1557-1560

[2] Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors [J].

Almohaywi, Basmah ;

Taunk, Aditi ;

Wenholz, Daniel S. ;

Nizalapur, Shashidhar ;

Biswas, Nripendra N. ;

Ho, Kitty K. K. ;

Rice, Scott A. ;

Iskander, George ;

Black, David StC. ;

Griffith, Renate ;

Kumar, Naresh .

MOLECULES, 2018, 23 (05)

[3] Copper-mediated Chan-Evans-Lam N-arylation of 5-methylene-4-aryl1,5-dihydro-2H-pyrrol-2-one derivatives [J].

Almohaywi, Basmah ;

Iskander, George ;

Yu, Tsz Tin ;

Bhadbhade, Mohan ;

Black, David St C. ;

Kumar, Naresh .

TETRAHEDRON LETTERS, 2018, 59 (09) :811-814

[4] Indole-based novel small molecules for the modulation of bacterial signalling pathways [J].

Biswas, Nripendra Nath ;

Kutty, Samuel K. ;

Barraud, Nicolas ;

Iskander, George M. ;

Griffith, Renate ;

Rice, Scott A. ;

Willcox, Mark ;

Black, David StC. ;

Kumar, Naresh .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2015, 13 (03) :925-937

[5] Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer [J].

Bottomley, Matthew J. ;

Muraglia, Ester ;

Bazzo, Renzo ;

Carfi, Andrea .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (18) :13592-13600

[6] Short and efficient synthesis of rubrolide E [J].

Chavan, Subhash P. ;

Pathak, Ashok B. ;

Pandey, Ankur ;

Kalkote, Uttam R. .

SYNTHETIC COMMUNICATIONS, 2007, 37 (22-24) :4253-4263

[7] Rh-catalyzed asymmetric hydrogenation of γ-phthalimido-substituted α,β-unsaturated carboxylic acid esters:: An efficient enantioselective synthesis of β-aryl-γ-amino acids [J].

Deng, Jun ;

Duan, Zheng-Chao ;

Huang, Jia-Di ;

Hu, Xiang-Ping ;

Wang, Dao-Yong ;

Yu, Sai-Bo ;

Xu, Xue-Feng ;

Zheng, Zhuo .

ORGANIC LETTERS, 2007, 9 (23) :4825-4828

[8] Putting Anion-π Interactions Into Perspective [J].

Frontera, Antonio ;

Gamez, Patrick ;

Mascal, Mark ;

Mooibroek, Tiddo J. ;

Reedijk, Jan .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (41) :9564-9583

[9]

FURSTNER A, 1989, SYNTHESIS-STUTTGART, P571

[10] Synthesis, quorum sensing inhibition and docking studies of 1,5-dihydropyrrol-2-ones [J].

Goh, Wai-Kean ;

Gardner, Christopher R. ;

Sekhar, Kondapalli V. G. Chandra ;

Biswas, Nripendra N. ;

Nizalapur, Shashidhar ;

Rice, Scott A. ;

Willcox, Mark ;

Black, David Stc. ;

Kumar, Naresh .

BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (23) :7366-7377

← 1 2 3 →