Abstract

MOLECULAR DOCKING STUDIES OF PYRIDINE-CARBOXAMIDE DERIVATIVES AS POTENTIAL ANTIPSYCHOTIC DRUG: MULTITARGETED DRUG APPROACH

Rajni Shah*, Saransh Shrivastava and Aparna Mandley

Abstract

Schizophrenia is a complex CNS disorder affecting 2 million people of the world’s population. It is characterized by distortions in multiple domains inclusive of perception, thinking, emotions, self sense, and behaviour. The various symptoms associated with schizophrenia are positive symptoms (delusions, hallucinations, and thought disorder); negative symptoms (alogia, affective flattening, anhedonia, avolition, and apathy) and cognitive dysfunction. Schizophrenia is associated with many different symptoms, developing the multi-target drugs with more than one pharmacological activity is an effective approach. For this approach the receptors involved in atypical antipsychotics (5- HT2A and D2) are the best chosen targets. Molecular docking studies were performed using Molegro Virtual Docker 6.0 to estimate the inhibition potential of these compounds. A series of novel pyridinecarboxamides (22 compounds) were docked against two targets: Dopamine D2 [PDB: 6CM4 (2.86Å)] and Serotonin 5-HT2A [PDB: 5A93 (3Å)]. Out of which 2 compounds 17c and 7c showed the best docking result on both the receptor as compared to the standard drug Resperidone.

Keywords: schizophrenia, molecular docking, dopamine (D2), serotonin (5-HT2A), multi- target drugs (MTDs).