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In- silico Design of Novel Inhibitors for 5-HT2A Receptor to Recuperate Schizophrenia

Richa Chaudhary, B N Mishra, Vivek Srivastava, Isha Chandra

Abstract


Schizophrenia is a mental disorder characterized by positive symptoms such as disorganized speech, delusions and hallucinations and negative symptoms such as deficits of attention, affective flattening and social withdrawal in nature. There are several receptor involve in schizophrenia, one of these 5-HT2A receptor i.e. serotonin receptor.  The serotonin receptor 5-HT2A has been involved in several neurological conditions and potent 5-HT2A inhibitors have therapeutic effects that use for the treatment of schizophrenia and depression. First and second generations of antipsychotics tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. In this study, 3D QSAR analysis using kNN-MFA method was performed on a series of benzathaizapine and pyrrolobenzezapine derivatives as 5-HT2A inhibiters and 5 potent novel 5-HT2A inhibitors discovered. Here, inhibition constants, Ki for 21 antipsychotics, which already approved for clinical treatment, the best model were evaluated using random selection method that use for the division dataset in to training and test set. kNN-MFA methodology with simulating annealing were used for the model building. The selected best QSAR model has training set of 17 molecules and test set of 4 molecules. Significant values of the cross-validated correlation q2 (0.77) and the fitted correlation r2 (0.95) revealed that this model have reasonable power to predict the biological affinity of new compound in interactions serotonin 5-HT2A receptor. The drug likeness of these molecules was checked through ADME property prediction.

 

 Keywords: Serotonin, 5-HT2A receptor, Schizophrenia

Cite this Article

Chaudhary Richa, Mishra B N,  Srivastava Vivek  et  al. In- silico Design of Novel Inhibitors for 5-HT2A Receptor to Recuperate Schizophrenia.  Research & Reviews: A Journal of Bioinformatics. 2015; 2(2): 11–17p


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