Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni
Jan Glaser,
Uta Schurigt,
Brian M. Suzuki,
Conor R. Caffrey,
Ulrike Holzgrabe
Affiliations
Jan Glaser
Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany
Uta Schurigt
Institute for Molecular Infection Biology, University of Wuerzburg, Josef-Schneider-Str. 2/D15, D-97080 Wuerzburg, Germany
Brian M. Suzuki
Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, 1700 4th St., San Francisco, CA 94158, USA
Conor R. Caffrey
Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, 1700 4th St., San Francisco, CA 94158, USA
Ulrike Holzgrabe
Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany
Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 1–30 for activity against schistosomula of Schistosoma (S.) mansoni. Compound 1 did not show any anti-schistosomal activity. However, strong phenotypic changes, including the formation of vacuoles, degeneration and death were observed after in vitro treatment with compounds 23 (thymyl cinnamate) and 27 (eugenyl cinnamate). Electron microscopy analysis of the induced vacuoles in the dying parasites suggests that 23 and 27 interfere with autophagy.