Synthesis, biological evaluation and 3D QSAR study of 2,4-disubstituted quinolines as anti-tuberculosis agents.
The synthesis and anti-tuberculosis activity for three series of 2,4-disubstituted quinolines is reported. The synthesized compounds were evaluated for activity against M. tuberculosis H37Rv strain; most promising compounds from the series exhibited MIC99 values ranged between 3.125 and 6.25 μg/mL. None of the compounds exhibited cytotoxicity up to the highest test concentration of 200 μg/mL. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by Comparative Molecular Field Analysis (CoMFA). Atom-fit alignment provided the best model, and allowed prediction of the activity of molecules in the test sets leading to the rationalization of the relationship between structure and activity.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
Sanjay R
SR
Patel
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
Rahul
R
Gangwal
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
Abhay T
AT
Sangamwar
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India. Electronic address: rahuljain@niper.ac.in.
Rahul
R
Jain
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000995:Antitubercular Agents; D011804:Quinolines
Homolytic free radical reaction; Ring-substituted quinolines; Synthesis; Tuberculosis