Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships.
Honaucins A-C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-γ-butyrolactone and 4-chlorocrotonic acid, which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of both bioluminescence, a quorum-sensing-dependent phenotype, in Vibrio harveyi BB120 and lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several proinflammatory cytokines, most dramatically interleukin-1β. Synthesis of honaucin A, as well as a number of analogs, and subsequent evaluation in anti-inflammation and quorum-sensing inhibition bioassays revealed the essential structural features for activity in this chemical class and provided analogs with greater potency in both assays.
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
Hyukjae
H
Choi
Samantha J
SJ
Mascuch
Francisco A
FA
Villa
Tara
T
Byrum
Margaret E
ME
Teasdale
Jennifer E
JE
Smith
Linda B
LB
Preskitt
David C
DC
Rowley
Lena
L
Gerwick
William H
WH
Gerwick
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D003437:Crotonates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000458:Cyanobacteria / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000276:immunology; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014733:Vibrio / Q000187:drug effects / Q000502:physiology; D014735:Vibrio Infections / Q000188:drug therapy
C511346:3-hydroxy-gamma-butyrolactone; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D003437:Crotonates; C575082:honaurin A; C575083:honaurin B; C575084:honaurin C; D009569:Nitric Oxide; D015107:4-Butyrolactone