Molecular Modeling Study on Diazine Indole Acetic Acid Derivatives for CRTH2 Inhibitory Activity

Title:Molecular Modeling Study on Diazine Indole Acetic Acid Derivatives for CRTH2 Inhibitory Activity

Volume: 19 Issue: 6

Author(s): Sathya Babu, Mottadi Rupa, Santhosh Kumar Nagarajan, Honglae Sohn and Thirumurthy Madhavan

Affiliation:

Keywords: CRTH2, Diazine indole acetic acid, Topomer CoMFA, HQSAR, CoMFA, CoMSIA.

Abstract: In the present work, molecular modeling studies have been reported on a series of diazine indole acetic acid derivatives to analyze the structure-activity relationship studies of CRTH2 using fragment (Topomer CoMFA and HQSAR) and field (CoMFA and CoMSIA) based QSAR methods. Twenty-six compounds were used as a training set to establish the model, and six compounds were used as a test set to validate the model. The generated models exhibited good statistical results such as correlation coefficient (r²) and the cross-validated correlation coefficient (q²). Topomer CoMFA analysis yielded the q² of 0.610 and r² of 0.981. HQSAR model generated using bond and connectivity as fragment distinction and 3-6 as fragment size has the q² value of 0.707 and conventional r² value of 0.892 with five components. CoMFA model was assessed by cross-validated q² value of 0.543 and r² value of 0.901 with steric and electrostatic fields. CoMSIA model generated using steric, hydrophobic and donor fields with q² value of 0.550 and r² value of 0.888 was found to be the optimal model among the various models generated. The contour maps were generated to analyze the important structural features that regulate their inhibitory potency. From the result of contour maps we have suggested the critical sites for chemical modification which will be useful in designing potent compounds with improved activity.

Cite this article as:

Babu Sathya, Rupa Mottadi, Nagarajan Kumar Santhosh, Sohn Honglae and Madhavan Thirumurthy, Molecular Modeling Study on Diazine Indole Acetic Acid Derivatives for CRTH2 Inhibitory Activity, Combinatorial Chemistry & High Throughput Screening 2016; 19 (6) . https://dx.doi.org/10.2174/1386207319666160502123759