title: Inhibition of quorum sensing in gram-negative bacteria by alkylamine-modified cyclodextrins.
abstract: N-Acylhomoserine lactones (AHLs) are used as quorum-sensing (QS) signals by gram-negative bacteria. We have reported that the cyclic oligosaccharides known as cyclodextrins (CDs) form inclusion complexes with AHLs and disrupt QS signaling. In this study, a series of CD derivatives were designed and synthesized to improve the QS inhibitory activity over that of native CDs. The production of the red pigment prodigiosin by Serratia marcescens AS-1, which is regulated by AHL-mediated QS, was drastically decreased by adding 10 mg/ml 6-alkylacylamino-β-CD with an alkyl chain ranging from C7 to C12. An improvement in the QS inhibitory activity was also observed for 6-alkylamino-α- or γ-CDs and 2-alkylamino-CDs. Furthermore, 6,6'-dioctylamino-β-CD, which contains two octylamino groups, exhibited greater inhibitory activity than 6-monooctylamino-β-CD. The synthesized CD derivatives also had strong inhibitory effects on QS by other gram-negative bacteria, including Chromobacterium violaceum and Pseudomonas aeruginosa. The synthetic alkylamine-modified CD derivatives had higher equilibrium binding constants for binding with AHL than the native CDs did, consistent with the improved QS inhibition. ¹H NMR measurements suggested that the alkyl side chains of 6-alkylacylamino-β-CDs with alkyl chains up to 6 carbon atoms long could form self-inclusion complexes with the CD unit.
authors: Department of Material and Environmental Chemistry, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585, Japan. morohosi@cc.utsunomiya-u.ac.jp
authors: Tomohiro
authors: T
authors: Morohoshi
authors: Kazuho
authors: K
authors: Tokita
authors: Satoshi
authors: S
authors: Ito
authors: Yuki
authors: Y
authors: Saito
authors: Saki
authors: S
authors: Maeda
authors: Norihiro
authors: N
authors: Kato
authors: Tsukasa
authors: T
authors: Ikeda
mesh_terms: D054742:Acyl-Butyrolactones / Q000737:chemistry*; D002861:Chromobacterium / Q000187:drug effects / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism; D011353:Prodigiosin / Q000096:biosynthesis; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects*; D012706:Serratia marcescens / Q000187:drug effects / Q000378:metabolism
chemical_list: D054742:Acyl-Butyrolactones; D003505:Cyclodextrins; D011353:Prodigiosin