title: Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni.
abstract: 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.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany. jan.glaser@uni-wuerzburg.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Glaser
authors.affiliation: Institute for Molecular Infection Biology, University of Wuerzburg, Josef-Schneider-Str. 2/D15, D-97080 Wuerzburg, Germany. uta.schurigt@arcor.de.
authors.forename: Uta
authors.initials: U
authors.lastname: Schurigt
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, 1700 4th St., San Francisco, CA 94158, USA. brian.suzuki@ucsf.edu.|Department of Pathology, University of California, San Francisco, CA 94158, USA. brian.suzuki@ucsf.edu.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Suzuki
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, 1700 4th St., San Francisco, CA 94158, USA. conor.caffrey@ucsf.edu.|Department of Pathology, University of California, San Francisco, CA 94158, USA. conor.caffrey@ucsf.edu.
authors.forename: Conor R
authors.initials: CR
authors.lastname: Caffrey
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany. u.holzgrabe@pharmazie.uni-wuerzburg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology*; D022162:Cytoplasmic Vesicles; D004353:Drug Evaluation, Preclinical; D004952:Esters; D012550:Schistosoma mansoni / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D012556:Schistosomicides / Q000737:chemistry* / Q000494:pharmacology*; D054852:Small Molecule Libraries
chemical_list: D002934:Cinnamates; D004952:Esters; D012556:Schistosomicides; D054852:Small Molecule Libraries; C029010:cinnamic acid
keywords: Schistosoma; anti-schistosomal activity; autophagy; eugenyl cinnamate; parasite; schistosomula; thymyl cinnamate; vacuoles