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-beta-CD with an alkyl chain ranging from C7 to C12. An improvement in the QS inhibitory activity was also observed for 6-alkylamino-alpha- or gamma-CDs and 2-alkylamino-CDs. Furthermore, 6,6'-dioctylamino-beta-CD, which contains two octylamino groups, exhibited greater inhibitory activity than 6-monooctylamino-beta-CD. The synthesized CD derivatives also had strong inhibitory effects on QS by other grain-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. H-1 NMR measurements suggested that the alkyl side chains of 6-alkylacylamino-beta-CDs with alkyl chains up to 6 carbon atoms long could form self-inclusion complexes with the CD unit. (c) 2013, The Society for Biotechnology, Japan. All rights reserved.