Antitrypanosomal sesquiterpene lactones from Saussurea costus Tasqiah Julianti a, c , Yoshie Hata a, d , Stefanie Zimmermann a, b , Marcel Kaiser b, e , Matthias Hamburger a , Michael Adams a, ⁎ a Division of Pharmaceutical Biology, University of Basel, CH-4056 Basel, Switzerland b Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland c Faculty of Pharmacy, Pancasila University, 12640 Jakarta, Indonesia d Department of Pharmacy, National University of Colombia, Carrera 30 45-03, Bogotá, Colombia e University of Basel, CH-4051 Basel, Switzerland article info abstract Article history: Received 12 April 2011 Accepted in revised form 12 May 2011 Available online 23 May 2011 In the course of a larger screen of 1800 plant and fungal extracts, the ethyl acetate extract of Saussurea costus roots potently inhibited the growth of Trypanosoma brucei rhodesiense. Subsequent HPLC based activity profiling led to the identification of the sesquiterpene lactones arbusculin B (1), α-cyclocostunolide (2), costunolide (3), and dehydrocostuslactone (4). They were tested for in vitro antitrypanosomal activities and cytotoxicity alongside the structurally related sesquiterpene lactones parthenolide (5), zaluzanin D (6), and eupatoriopicrin (7), and had IC 50 s between 0.8 and 22 μM. Cytotoxic IC 50 s were from 1.6 to 19 μM, and selectivity indices from 0.5 to 6.5. © 2011 Elsevier B.V. All rights reserved. Keywords: Saussurea costus Asteraceae Sesquiterpene lactones Trypanosoma brucei rhodesiense HPLC-based activity profiling 1. Introduction The fragrant roots of Saussurea costus (Falc.) Lipschitz (Asteraceae), synonym: Saussurea lappa C.B. Clarke, have been used for thousands of years as medicines, incenses and ointments by many cultures. In India they are called Kur or Kushtha, and in China Yún mù xiāng (云木香). In the Ayurveda, Siddha, and Unani medicinal systems S. costus roots are used alone or in combination with other drugs to treat asthma, cholera, chronic skin diseases, rheumatism, cough and cold, quartan malaria, leprosy, persistent hiccups, rheumatism, stomach-ache, toothache, and typhoid fever [1,2]. A broad spectrum of biological activities such as anti- inflammatory, anticancer, immunomodulatory, CNS depres- sant, and antimicrobial properties have been reported for S. costus extracts [3–5]. Activities have commonly been related to the presence of sesquiterpene lactones. Furthermore, tannins, steroids, alkaloids, glycosides, terpenoids, flavonoids, peptides, and organic acids have been reported from this plant [3,4]. Our interest in this plant was raised when we performed an antiprotozoal screen of 1800 plant and fungal extracts for effects against the parasites Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Plasmodium falciparum and Leishmania donovani, the causal agents of human African trypanosomi- asis, Chagas disease, malaria, and leishmaniasis, respectively [6–8]. Amongst the most potent extracts in this screen was an ethyl acetate extract of S. costus roots which inhibited T. b. rhodesiense by 96% at a test concentration of 4.8 μg/ml. HPLC based activity profiling was used to identify the active constituents in the extract. In this approach sub- milligramme amounts of extract are separated by analytical scale HPLC and automatically fractionated into 96 well plates. The microfractions obtained are submitted to the bioassay, and the resulting activity profile can be overlaid with the HPLC trace to correlate peaks of activity with peaks in the HPLC chromatogram. On-line spectroscopic data (UV–Vis and MS) collected during separation, combined with database Fitoterapia 82 (2011) 955–959 ⁎ Corresponding author at: Institute of Pharmaceutical Sciences, Division of Pharmaceutical Biology University of Basel, CH-4056 Basel, Switzerland. Fax: +41 61 267 1474. E-mail address: michael.adams@unibas.ch (M. Adams). 0367-326X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.fitote.2011.05.010 Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote