Quantitative Structure − Antiprotozoal Activity Relationships of Sesquiterpene Lactones †

Molecules

Thomas J. Schmidt¹  Amal M. M. Nour¹  Sami A. Khalid³  Marcel Kaiser² 

[1] Westfälische Wilhelms-Universität Münster, Institut für Pharmazeutische Biologie und Phytochemie, Hittorfstraße 56, D-48149 Münster, Germany; E-mails:;Swiss Tropical Institute (STI), Socinstrasse 57, CH-4002 Basel, Switzerland;E-mails:;University of Khartoum, Department of Pharmacognosy, Faculty of Pharmacy, P.O. box 1996, Khartoum, Sudan; E-mail:

关键词: Trypanosoma;    Leishmania;    Plasmodium;    antiprotozoal activity;    sesquiterpene lactone;    QSAR;   

DOI  :  10.3390/molecules14062062

来源: mdpi

【 摘 要 】

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 known to be essential for other biological activities of STLs. It was observed, however, that certain compounds are considerably more toxic against protozoa than against mammalian cells while others are more cytotoxic than active against the protozoa. A comparative QSAR analysis was therefore undertaken, in order to discern the antiparasitic activity of STLs against T. brucei and cytotoxicity. Both activities were found to depend to a large extent on the same structural elements and molecular properties. The observed variance in the biological data can be explained in terms of subtle variations in the relative influences of various molecular descriptors.

【 授权许可】

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© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.