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QSAR Studies on Antiepileptic and Locomotor in vivo Activities of 4,5‐diphenyl‐1H‐Imidazoles
Author(s) -
Puratchikody Ayarivan,
Doble Mukesh
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00837.x
Subject(s) - quantitative structure–activity relationship , training set , test set , in vivo , chemistry , polar , polar surface area , locomotor activity , principal component analysis , molecular descriptor , solvent , imidazole , molecule , stereochemistry , computational chemistry , mathematics , artificial intelligence , computer science , pharmacology , organic chemistry , biology , physics , statistics , astronomy , microbiology and biotechnology
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 ?51% and 50% correlated to locomotor and antiepileptic activities respectively.