3D-QSAR study of ring-substituted quinoline class of anti-tuberculosis agents.
A 3D-QSAR analysis of a new class of ring-substituted quinolines with anti-tuberculosis activity has been carried out by three methods-Comparative Molecular Field Analysis (CoMFA), CoMFA with inclusion of a hydropathy field (HINT), and Comparative Molecular Similarity Indices Analysis (CoMSIA). The conformation of the molecules was generated using a simulated annealing protocol and they were superimposed using features common to the set with database alignment (SYBYL) and field fit methods. Several statistically significant CoMFA, CoMFA with HINT, and CoMSIA models were generated. Prediction of the activity of a set of test molecules was the best for the CoMFA model generated with database alignment. Based upon the information contained in the CoMFA model, we have identified some novel features that can be incorporated into the quinoline framework to improve the activity.
Nayyar
Amit
A
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Malde
Alpeshkumar
A
Jain
Rahul
R
Coutinho
Evans
E
D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D016208:Databases, Factual; D016018:Least-Squares Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D055672:Static Electricity; D013816:Thermodynamics
D000995:Antitubercular Agents; D011804:Quinolines