title: Antitrypanosomal structure-activity-relationship study of synthetic cynaropicrin derivatives.
abstract: Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure-activity-relationship (SAR) study against T. brucei is described.
authors.affiliation: Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan. Electronic address: t-usuki@sophia.ac.jp.
authors.forename: Toyonobu
authors.initials: T
authors.lastname: Usuki
authors.affiliation: Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors.forename: Shihori
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshimoto
authors.affiliation: Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kondo
authors.affiliation: Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
authors.affiliation: Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Adams
mesh_terms: D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; D014344:Trypanocidal Agents; C075687:cynaropicrin
keywords: Cynaropicrin; Derivatization; Guaianolide; SAR; Trypanosoma brucei