3D-QSAR and docking studies on a series of benzothiadiazine derivatives as genotype 1 HCV polymerase inhibitors.
The Benzothiadiazine derivatives have been regarded as a novel class of HCV genotype 1 polymerase inhibitors. To explore the relationship between the structures of substituted Benzothiadiazine derivatives and their inhibitory activities against HCV, 3D-QSAR and molecular docking studies were performed on a dataset of ninty-eight compounds. The 3D-QSAR models resulted from seventy-eight molecules in the training set gave q(2) value of 0.81 and a test set of twenty compounds, gave predictive r(2) value of 0.94. 3D-QSAR model generated from kNN-MFA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel HCV genotype 1 inhibitors with better potencies.
School of Pharmacy, Bharat Institute of Technology, Meerut-250 005 (UP) India. vaishalimasand@hotmail.com
Vaishali M
VM
Patil
Satya Prakash
SP
Gupta
Subeer
S
Samanta
Neeraj
N
Masand
D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001581:Benzothiadiazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship
D000998:Antiviral Agents; D001581:Benzothiadiazines; D004791:Enzyme Inhibitors; D012321:DNA-Directed RNA Polymerases