Design, synthesis and activity evaluation study of novel substituted N-sulfonyl homoserine lactone derivatives as bacterial quorum sensing inhibitors
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A novel series of N-sulfonyl homoserine lactone derivatives 7a–7m has been designed, synthesized, and evaluated for quorum sensing inhibitory activities through the violacein inhibition in Chromobacterium violaceum CV026. Compound 7e displayed the high level of inhibitory activity among all the compounds synthesized. Studies of structure-activity relationship indicated that compounds with thiophene group in side chain showed better activity than those substituted by furan, pyrrole, pyridyl, and phenethyl group. Thiophene substituted compounds which connected electron withdrawing group exhibited better inhibitory activity relate to those connected electron donating group. Further analysis indicated that compound bearing an electron withdrawing substituent at the position 2 of their thiophene ring exhibited superior activity against violacein production to those bearing the substituent at the position 3 and 4. Compound 7e in particular, with IC50 value of 6.19 µM, were identified as promising lead compounds for further development.
KeywordsBacterial quorum sensing inhibitor Acylhomoserine lactone Design Synthesis Activity evaluation
This work was supported by Chinese national science foundation with Grant No. 81274182, 81573687.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no competing interests.
- McClean KH, Winson MK, Fish L, Taylor A, Chhabra SR, Camara M, Daykin M, Lamb JH, Swift S, Bycroft BW, Stewart GS, Williams P (1997) Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology 143:3703–3711CrossRefPubMedGoogle Scholar
- Nielsen J, Givskov M (2003) Compounds and Methods for controlling bacterial virulence field of the invention. WO03/106445 A1, 24 December 2003.Google Scholar
- Olivero JT, Pájaro NP, Stashenko E (2011) Antiquorum sensing activity of essential oils isolated from different species of the genus piper. Vitea revista de la facultad de quimica farmaceutica 18:2145–2166Google Scholar
- Sabbah M, Fanny F, Grand L, Boukraa M, Efrit ML, Doutheau A, Soulère L, Queneau Y (2012) Synthesis and biological evaluation of new N-acyl-homoserine-lactone analogues, base on triazole and tetrazole scaffolds, acting as LuxR-dependent quorum sensing modulators. Bioorg Med Chem 20:4727–4736CrossRefPubMedGoogle Scholar