In Silico Identification of Novel HDAC2 Inhibitors for Reinstating Synaptic wiring in Autism Spectrum Disorder

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an increasing incidence rate. For the treatment of ASD, several pharmaceutical approaches, dietary supplements, and behavioral therapy have been proposed, but a definitive cure remains elusive. Histone deacetylases (HDACs) are critical epigenetic regulators whose molecular and pharmacological roles are being studied extensively in medically significant ailments such as neuropsychiatric disorders, neurodegenerative diseases, and cancer on a global scale. HDAC2's specific expression pattern in CNS makes it an appealing therapeutic target for neurological illnesses such as ASD.Methods: The study used PyRx software (version 0.8) to screen a library of 401 alkaloid compounds against HDAC2. In addition, the DS software was used to predict the physicochemical and DMET properties of the compound library.Results: Valaciclovir hydrochloride, Dihydrocapsaicin, Guanosine, Santacruzamate A, and 2'-Deoxyguanosine monohydrate compounds exhibited strong interactions with HDAC2. These compounds had a higher binding energy than the control compound, and they have promising drug-like properties and ADMET characteristics.Conclusion: These identified compounds could be used as HDAC2 inhibitors for the management of ASD, however, experimental research is needed to optimize them as HDAC2 inhibitors.Keywords: Autism spectrum disorder; Histone deacetylases; Alkaloid compounds; Drug-likeness