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- Title
CoMFA and CoMSIA 3D-QSAR analysis of diaryloxy-methano-phenanthrene derivatives as anti-tubercular agents.
- Authors
Shagufta; Ashutosh Kumar; Gautam Panda; Mohammad Siddiqi
- Abstract
AbstractComparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were conducted on a series (44 compounds) of diaryloxy-methano-phenanthrene derivatives as potent antitubercular agents. The best predictions were obtained with a CoMFA standard model (q2=0.625,r2=0.994) and with CoMSIA combined steric, electrostatic, and hydrophobic fields (q2=0.486,r2=0.986). Both models were validated by a test set of seven compounds and gave satisfactory predictiver2values of 0.999 and 0.745, respectively. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands to account for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, and hydrophobic fields. The information obtained from CoMFA and CoMSIA 3-D contour maps can be used for further design of phenanthrene-based analogs as anti-TB agents. The resulting contour maps, produced by the best CoMFA and CoMSIA models, were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction-field contour maps also showed a high level of internal consistency. This study suggests that introduction of bulky and highly electronegative groups on the basic amino side chain along with decreasing steric bulk and electronegativity on the phenanthrene ring might be suitable for designing better antitubercular agents.
- Subjects
QSAR models; STRUCTURE-activity relationships; PHENANTHRENE; ANTITUBERCULAR agents
- Publication
Journal of Molecular Modeling, 2007, Vol 13, Issue 1, p99
- ISSN
1610-2940
- Publication type
Article
- DOI
10.1007/s00894-006-0124-0