Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships

Hyukjae Choi; Samantha J Mascuch; Francisco A Villa; Tara Byrum; Margaret E Teasdale; Jennifer E Smith; Linda B Preskitt; David C Rowley; Lena Gerwick; William H Gerwick

doi:10.1016/j.chembiol.2012.03.014

Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships

Chem Biol. 2012 May 25;19(5):589-98. doi: 10.1016/j.chembiol.2012.03.014.

Authors

Hyukjae Choi¹, Samantha J Mascuch, Francisco A Villa, Tara Byrum, Margaret E Teasdale, Jennifer E Smith, Linda B Preskitt, David C Rowley, Lena Gerwick, William H Gerwick

Affiliation

¹ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

4-Butyrolactone / analogs & derivatives*
4-Butyrolactone / chemistry
4-Butyrolactone / isolation & purification
4-Butyrolactone / pharmacology
Animals
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / pharmacology
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology
Cell Line
Crotonates / chemistry*
Crotonates / isolation & purification
Crotonates / pharmacology
Cyanobacteria / chemistry*
Macrophages / drug effects
Macrophages / immunology
Mice
Molecular Sequence Data
Nitric Oxide / immunology
Quorum Sensing / drug effects*
Structure-Activity Relationship
Vibrio / drug effects
Vibrio / physiology
Vibrio Infections / drug therapy

Substances

3-hydroxy-gamma-butyrolactone
Anti-Bacterial Agents
Anti-Inflammatory Agents
Crotonates
honaurin A
honaurin B
honaurin C
Nitric Oxide
4-Butyrolactone

Associated data

GENBANK/GU111930

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding