TY  - JOUR
AB  - Three complementary quantitative structure–activity relationship (QSAR) methodologies, namely, regression modeling based on (i) “classical” molecular descriptors, (ii) 3D pharmacophore features, and (iii) 2D molecular holograms (HQSAR) were employed on the antitrypanosomal activity of sesquiterpene lactones (STLs) toward Trypanosoma brucei rhodesiense (Tbr), the causative agent of the East African form of human African trypanosomiasis. In this study, an extension of a previous QSAR study on 69 STLs, models for a much larger and more diverse set of such natural products, now comprising 130 STLs of various structural subclasses, were established. The extended data set comprises a variety of STLs isolated and tested for antitrypanosomal activity within our group and is furthermore enhanced by 12 compounds obtained from literature, which have been tested in the same laboratory under identical conditions. Detailed QSAR analyses yielded models with comparable and 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 reactive enone groups within the molecular structure but is influenced by their hydrophilic/hydrophobic properties and molecular shape.
AU  - Kimani, Njogu Mark
AU  - Matasyoh, Josphat C.
AU  - Kaiser, Marcel
AU  - Nogueira, Mauro S.
AU  - Trossini, Gustavo H. G.
AU  - Schmidt, Thomas J.
DA  - 2018-11-22
DO  - 10.3390/ijms19123721
KW  - QSAR
KW  - sesquiterpene lactones
KW  - Trypanosoma brucei
KW  - human African trypanosomiasis
KW  - pharmacophore-based drug design
LA  - eng
N1  - International Jouornal of Molecular Sciences 19 (2018) 3721, 1-22
N1  - Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2018-11-22
TI  - Complementary Quantitative Structure–Activity Relationship Models for the Antitrypanosomal Activity of Sesquiterpene Lactones
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-06169598451
Y2  - 2024-11-24T18:10:16
ER  -