title: Synthesis, biological evaluation and 3D-QSAR study of hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline as anti-tuberculosis agents.
abstract: We report synthesis, anti-tuberculosis activity and 3D-QSAR study of forty nine hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline. The most potent compounds upon evaluation for anti-tuberculosis activity exhibited MIC99 of 3.125 μg/mL against Mycobacterium tuberculosis H37Rv strain. We applied the in silico technique of 3D-QSAR to study structure activity relationship of the synthesized compounds. The developed CoMFA model exhibited excellent r(2)ncv of 0.971, and r(2)cv of 0.543. The predicted r(2)pred of 0.883 showed that the predicted values were in good agreement with the experimental values. Further, the contour map analysis, suggested that the sterically bulky and electronegative substitutions at the para position of the phenyl ring are favorable for anti-tuberculosis activity.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Gangwal
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
authors.forename: Abhay T
authors.initials: AT
authors.lastname: Sangamwar
authors.affiliation: 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.
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D006834:Hydrazines / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; 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*; D012663:Semicarbazides / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D006834:Hydrazines; D011804:Quinolines; D012663:Semicarbazides; C005151:thiosemicarbazide; D000218:Adamantane
keywords: CoMFA; Hydrazide; Quinolines; Semicarbazide; Thiosemicarbazide; Tuberculosis