Abstract
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.
Medicinal Chemistry
Title:Structure-Activity Relationships of Pyrrole Hydrazones as New Anti-Tuberculosis Agents
Volume: 8 Issue: 3
Author(s): Iglika Lessigiarska, Ilza Pajeva, Penka Prodanova, Maya Georgieva and Atanas Bijev
Affiliation:
Keywords: Classification trees, hydrazones, pharmacophore, pyrrole, QSAR, tuberculostatics, pyrrole hydrazones, molecular flexibility, H-bond, metal ligator.
Abstract: 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.
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Lessigiarska Iglika, Pajeva Ilza, Prodanova Penka, Georgieva Maya and Bijev Atanas, Structure-Activity Relationships of Pyrrole Hydrazones as New Anti-Tuberculosis Agents, Medicinal Chemistry 2012; 8 (3) . https://dx.doi.org/10.2174/1573406411208030462
DOI https://dx.doi.org/10.2174/1573406411208030462 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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