Abstract
Aim: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. Results: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability. The CED-10(Rac-1)/PAK1 pathway was essential for immunomodulation by CAPE and was a critical component involved in the immune response to fungal pathogens. Conclusion: Caenorhabditis elegans is an efficient heterologous host to evaluate immunomodulatory compounds and identify components of the pathway(s) involved in the mode of action of compounds.
Original language | English (US) |
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Pages (from-to) | 2033-2046 |
Number of pages | 14 |
Journal | Future Medicinal Chemistry |
Volume | 8 |
Issue number | 17 |
DOIs | |
State | Published - Nov 2016 |
Keywords
- caffeic acid phenethyl ester
- Candida
- innate immune response
- p21 kinase
- propolis
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery