engleski

Advances in QSAR analysis of anti-trypanosomal activity

Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease transmitted by tsetse fly (Glossina genus) and caused by kinetoplastid Trypanosoma. We have investigated quantitative structure–activity relationship (QSAR) of anti-trypanosomal activities of natural compounds polyphenols [1], as well as synthetic compounds: pyridyl benzamides, 3-(oxazolo [4, 5-b]pyridin-2- yl)anilides[2], and 6-arylpyrazine-2- carboxamides [3]. Anti-trypanosomal activity was modelled by using mono-dimensional (1D), to three-dimensional molecular (3D) descriptors. In order to find a thriving QSAR models for anti-trypanosomal activities, genetic algorithm-multilinear regression (GA-MLR) and artificial neural networks (ANN) were employed. The GA-MLR QSAR models have excellent statistical robustness with good external predictive ability. For the polyphenols, the obtained models displayed relevance of the frequency of occurrence of two oxygen atoms at topological distance, as well as stability of molecules. The most relevant structural features for the pyridyl benzamides is the presence of oxygen-halogen at a topological distance 6. Derivatives of 3-(oxazolo[4, 5- b]pyridin-2-yl)anilide with enhanced anti- trypanosomal activities should have furan ring and atoms at a topological distance of 7. Inhibitory activity of 6-arylpyrazine-2- carboxamides has correlation with the presence of N-sec-butylformamide and substituted benzene. The results obtained will be useful for further research of more effective plant- derived agents and future synthesized compounds against the Trypanosoma.

QSAR ; anti-trypanosomal activity

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