QSAR Studies on Antiepileptic and Locomotorin vivoActivities of 4,5‐diphenyl‐1H‐Imidazoles
Ayarivan Puratchikody, Mukesh Doble · Chemical Biology & Drug Design · 2009
This paper describes the pharmacological evaluation pertaining to in vivo antiepileptic and locomotor activities, and subsequent QSAR studies on 4,5-diphenyl-1H-imidazole analogues. These two activities on albino mice were determined based on electroshock method and by using actophotometer respectively. Compounds with 4-fluorophenyl, 4-dimethylaminophenyl, 4-hydroxyphenyl and 4-methoxyphenyl substitutions exhibit the highest activity. Compounds with phenyl and 2-nitrophenyl substitutions exhibit the lowest activity in both the cases. Data are divided into training and test/validation sets, the former is used for developing the QSAR and the latter is used for determining the predictive capability of the developed models. The three-parameter model for the antiepileptic activity fits the data well and has a good predictive capability (For training set: R( 2) = 0.77, R( 2)(adj) = 0.72, q( 2) = 0.64, R( 2)(mod)= 0.66, for test set: R( 2) = 0.75). Total polar and solvent-accessible surface areas of the molecule are the descriptors in the model. A three parameter model and a four-parameter model for the locomotor activity fit the data well and have good predictive capability (For training set: R( 2) = 0.8-0.89, R( 2)(adj) = 0.76-0.77, q (2) = 0.7-0.86, R( 2)(mod)= 0.64-0.85, for test set: R( 2) = 0.79-0.9). Molecule shape, solvent-accessible surface area, LUMO and polar surface area are the significant descriptors. The first principal component is reverse similar51% and 50% correlated to locomotor and antiepileptic activities respectively.