Quantitative Structure ？ Antiprotozoal Activity Relationships of Sesquiterpene Lactones 英文参考文献.docVIP

Molecules 2009, 14, 2062-2076; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Quantitative Structure ? Antiprotozoal Activity Relationships of Sesquiterpene Lactones ? Thomas J. Schmidt 1,*, Amal M. M. Nour 1, Sami A. Khalid 2, Marcel Kaiser 3 and Reto Brun 3 1 Westf?lische Wilhelms-Universit?t Münster, Institut für Pharmazeutische Biologie und Phytochemie, Hittorfstra?e 56, D-48149 Münster, Germany; E-mails: amal_mukhtar@ (A-M.N.) 2 University of Khartoum, Department of Pharmacognosy, Faculty of Pharmacy, P.O. box 1996, Khartoum, Sudan; E-mail: khalidseek@ (S.K.) 3 Swiss Tropical Institute (STI), Socinstrasse 57, CH-4002 Basel, Switzerland; E-mails: Marcel.Kaiser@unibas.ch (M.K.), Reto.Brun@unibas.ch (R.B.) ? This work is cordially dedicated to G. Willuhn, Düsseldorf, on the occasion of his 75th birthday * Author to whom correspondence should be addressed; E-mail: thomschm@uni-muenster.de Received: 12 May 2009; in revised form: 4 June 2009 / Accepted: 5 June 2009 / Published: 8 June 2009 Abstract: Prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (STLs) against Trypanosoma brucei rhodesiense (which causes East African sleeping sickness), we have now conducted a structure-(in-vitro)- activity study on a set of 40 STLs against T. brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Furthermore, cytotoxic activity against L6 rat skeletal myoblast cells was assessed. Some of the compounds possess high activity, especially against T. brucei (e.g. helenalin and some of its esters with IC50-values of 0.05- 0.1 μM, which is about 10 times lower than their cytotoxic activity). It was found that all investigated antiprotozoal activities are significantly correlated with cytotoxicity and the major determinants for activity are α,β-unsaturated structural elements, also k