1298024-16-4Relevant academic research and scientific papers
Immunosuppressive but non-LasR-inducing analogues of the pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)-l-homoserine Lactone
Jadhav, Gopal P.,Chhabra, Siri Ram,Telford, Gary,Hooi, Doreen S. W.,Righetti, Karima,Williams, Paul,Kellam, Barrie,Pritchard, David I.,Fischer, Peter M.
, p. 3348 - 3359 (2011/07/08)
Figure Presented. The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (1) is involved not only in bacterial activation but also in subversion of the host immune system, and this compound might thus be used as a template to design immunosuppressive agents, provided derivatives devoid of quorum-sensing activity could be discovered. By use of a leukocyte proliferation assay and a newly developed bioluminescent P. aeruginosa reporter assay, systematic modification of 1 allowed us to delineate the bacterial LasR-induction and host immunosuppressive activities. The main determinant is replacement of the methylene group proximal to the β-ketoamide in the acyl chain of 1 with functions containing heteroatoms, especially an NH group. This modification can be combined with replacement of the homoserine lactone system in 1 with stable cyclic groups. For example, we found the simple compound N1-(5-chloro-2-hydroxyphenyl)-N 3-octylmalonamide (25d) to be over twice as potent as 1 as an immune suppressor while displaying LasR-induction antagonist activity.
