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An extended study on quantitative structure-antitrypanosomal activity relationships of sesquiterpene lactones
* 1 , 2 , 3 , 4 , 5 , 4
1  Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, Münster D-48149, Germany
2  Department of Chemistry, Egerton University, P.O. Box 536, Egerton 20115, Kenya
3  Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, Basel CH-4051, Switzerland
4  Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Muenster, PharmaCampus Corrensstrasse 48, Muenster D-48149, Germany
5  Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Lineu Prestes, 580, 05508-000 São Paulo, Brazil

Published: 31 October 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session Posters

In continuation of a previous quantitative structure-activity relationship (QSAR) study on the antitrypanosomal activity of 69 sesquiterpene lactones (STLs) towards Trypanosoma brucei rhodesiense (Tbr) [1], the causative agent of East African form of human African trypanosomiasis, a QSAR model for a much larger and more diverse set of almost twice as many (130) of such natural products was established in this study. The extended data set has been obtained through a variety of STLs isolated and tested for antitrypanosomal activity within our group and further enhanced by 12 compounds obtained from literature, which have been tested in the same laboratory under identical conditions. Detailed QSAR analyses using various complementary approaches: (1) “Classical” descriptor-based QSAR using a genetic algorithm to select the most relevant variables, i.e. the same approach as in our previous study [1], (2) indicator variables deduced from pharmacophore features obtained from a 3D alignment of the most active molecules as applied in [2] and (3) hologram QSAR (HQSAR) based on molecular fingerprints of fragments extracted from the 2D molecular structure as used, e.g., in [3], have yielded models with good internal and external predictive ability. For a set of compounds as chemically diverse as the one under study, the models exhibited good coefficients of determination (R2) ranging from 0.71 to 0.85, as well as internal (leave-one-out Q2 values ranging from 0.62 to 0.72) and external validation coefficients (P2 values ranging from 0.54 to 0.73). The contributions of the various tested descriptors to the generated models are in good agreement with the results of previous QSAR studies and corroborate the fact that the antitrypanosomal activity of STLs is very much dependent on the presence and relative position of conjugated carbonyl groups within the molecular structure, but influenced by their hydrophilic/hydrophobic property and molecular shape


  1. Schmidt, T. J. et al. Antimicrob. Agents Chemother. 2014, 58 (1), 325–332.
  2. Schomburg, C. et al. Eur. J. Med. Chem. 2013, 63, 313–320.
  3. Trossini, G. H. G. et al. Molecules 2014, 19 (7), 10546–10562.
Keywords: sesquiterpene lactones; Trypanosoma brucei; human African trypanosomiasis; pharmacophore-based drug design