Antitrypanosomal structure-activity-relationship study of synthetic cynaropicrin derivatives

Toyonobu Usuki; Makiko Sato; Shihori Hara; Yukiko Yoshimoto; Ryosuke Kondo; Stefanie Zimmermann; Marcel Kaiser; Reto Brun; Matthias Hamburger; Michael Adams

doi:10.1016/j.bmcl.2013.12.099

Antitrypanosomal structure-activity-relationship study of synthetic cynaropicrin derivatives

Bioorg Med Chem Lett. 2014 Feb 1;24(3):794-8. doi: 10.1016/j.bmcl.2013.12.099. Epub 2014 Jan 2.

Authors

Affiliations

¹ 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.
² Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
³ 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.
⁴ Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
⁵ Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.

PMID: 24433861
DOI: 10.1016/j.bmcl.2013.12.099

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.

Keywords: Cynaropicrin; Derivatization; Guaianolide; SAR; Trypanosoma brucei.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Inhibitory Concentration 50
Lactones / chemical synthesis
Lactones / chemistry*
Lactones / pharmacology*
Molecular Structure
Sesquiterpenes / chemical synthesis
Sesquiterpenes / chemistry*
Sesquiterpenes / pharmacology*
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry*
Trypanocidal Agents / pharmacology*
Trypanosoma brucei brucei / drug effects*

Substances

Lactones
Sesquiterpenes
Trypanocidal Agents
cynaropicrin