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CoMFA, HQSAR, Pharmacophore and Docking studies on Pyridine analogs of nimesulide as Anti-Inflammatory Agents

Author Affiliations

  • 1 School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Khandwa Road, Indore-452017, MP, INDIA

Res. J. Recent Sci., Volume 4, Issue (IYSC-2015), Pages 97-104, September,2 (2015)


The anti-inflammatory and antipyretic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are brought about by blockade of production of prostaglandins from arachidonic acid through inhibition of cyclooxygenase (COX) enzyme. Molecular modeling studies were performed on a dataset of 22 pyridinic analogs of nimesulide. The dataset was divided into a training set consisting of 16 and a test set comprising of 6 compounds on random basis. The COX-1 activity expressed in IC50 was converted into pIC50 and used as a dependent variable in the QSAR study. The molecular modeling studies were performed using SYBYL X 2.0 software running on a core-2 duo Intel processor workstation. The CoMFA model displayed good statistical significance in terms of internal cross validation (q2) 0.458 and non-cross validation (r2) 0.982 respectively. Also, the predicted r2 values (r2 pred) of 0.77 for the test set for the developed model suggested significant predicting ability of the models. In the HQSAR analysis, better statistical results were obtained in fragment size 57 and A/B/C/H distinct (q2 0.987). Partial least square regression studies were performed by using COX inhibitory activity as dependent variable and structural properties of CoMFA and HQSAR as independent variables. Also, PLS of CoMFA was carried out with additional descriptors like ClogP, CMR and total dipole. Pharmacophore was developed using Galahad module of Sybyl and seven pharmacophoric features were depicted in molecules. The docking studies were carried out on pdb 1CQE (COX-1 with Flurbiprofen) and the interaction was obtained with Arg120. The studies revealed the importance of nitrogen as linker and triflouromethanesulfonamido group attached to pyridine ring.


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