Preliminary investigations of our research team have shown that some pyrrole hydrazones posses strong inhibitory activity against the tuberculosis bacilli, and thus represent a new perspective for development of anti-tuberculosis agents.
In this work the anti-tuberculosis activity of an in-house series of pyrrole hydrazones was investigated by quantitative structure-activity relationships (QSAR) analysis and by pharmacophore modelling. Different constitutional, topological, physicochemical, and quantum-mechanical descriptors of the chemical structure were calculated. The QSAR models included the number of chlorine, fluorine and nitrogen atoms, molecular flexibility and shape indexes, and magnitudes of charged molecular surfaces areas and hydrophobic volumes, suggesting importance of these structural characteristics for the activity. Next, a pharmacophore analysis was applied. A possible pharmacophore responsible for the compound interactions with their biological target in the 3D space consisted of five features, including hydrophobic centres, a potential H-bond acceptor and a potential metal ligator.
Keywords: Classification trees, hydrazones, pharmacophore, pyrrole, QSAR, tuberculostatics, pyrrole hydrazones, molecular flexibility, H-bond, metal ligator.
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