VIRTUAL SCREENING OF NEWER POTENTIAL COLONY STIMULATING FACTOR 1 INHIBITORS AS POTENT ANTIEPILEPTIC AGENTSAbstract
Background: Epilepsy is a chronic disorder that causes unprovoked, recurrent seizures like a sudden rush of electrical activity in the brain. Neuronal hyperexcitability in epilepsy is due to an imbalance between glutamate-mediated excitation and GABA-mediated inhibition. Aim: This prompted us to design newer CSF1R inhibitors as efficient therapeutic drugs for the treatment of epilepsy. Materials and Methods: Based on the common pharmacophoric features for the inhibition of CSF1R inhibitors, a series of leads were designed using computational methods. A virtual library consisting of newly designed 60 molecules as CSF¬1R inhibitors were constructed .Based on these facts, a virtual library has been generated with 60 newly designed ligands containing imidazole, benzo pyrrole, quinoline, oaxzole, quinoxaline, benzimidazole, heterocyclic nucleus as CSF1R inhibitors (60). The binding mechanism of newly designed ligands with target enzymes CSF1R inhibitors was studied using Auto dock tools 1.5.6. Conclusion: The designed compounds were subjected and filtered by applying ADMET properties. In comparison with docking scores of standard antiepileptic drugs vigabatrin (GABA-2.14, CSF1R-1, 31) and sodium valproate (GABA-3.19, CSF1R-3.6) and the newly designed ligands, CS1 (-6.61), CS3 (-6.22), CS14 (-6.04) were found to be highly active hits than that of standards.
R. Priyadharsini * A. Dharuman, P. Nithya, P. Shalini and G. Sumithra
College of Pharmacy, Madras Medical College, Chennai, Tamil Nadu, India.
09 September 2019
28 December 2020
18 February 2021
01 March 2021