title: Pharmacophore generation, atom-based 3D-QSAR, HQSAR and activity cliff analyses of benzothiazine and deazaxanthine derivatives as dual A2Aantagonists/MAO‑B inhibitors.
abstract: Dual inhibition of A2Aand MAO-B is an emerging strategy in neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) and hologram quantitative structure-activity relationship (HQSAR) models were generated with benzothiazine and deazaxanthine derivatives. Based on activity against A2Aand MAO-B, two statistically signiﬁcant 3D-QSAR models (r2= 0.96, q2= 0.76 and r2= 0.91, q2= 0.63) and HQSAR models (r2= 0.93, q2= 0.68 and r2= 0.97, q2= 0.58) were developed. In an activity cliff analysis, structural outliers were identified by calculating the Mahalanobis distance for a pair of compounds with A2Aand MAO-B inhibitory activities. The generated 3D-QSAR and HQSAR models, activity cliff analysis, molecular docking and dynamic studies for dual target protein inhibitors provide key structural scaffolds that serve as building blocks in designing drug-like molecules for neurodegenerative diseases.
authors.affiliation: a Department of Chemical Technology , University of Calcutta , Kolkata , West Bengal , India.
authors.forename: S S
authors.initials: SS
authors.lastname: Bhayye
authors.affiliation: b Department of Pharmaceutical Technology , Jadavpur University , Kolkata , West Bengal , India.
authors.forename: K
authors.initials: K
authors.lastname: Roy
authors.affiliation: a Department of Chemical Technology , University of Calcutta , Kolkata , West Bengal , India.
authors.forename: A
authors.initials: A
authors.lastname: Saha
keywords: Alzheimer’s disease; Dual targeting; HQSAR; Parkinson’s disease; activity cliff analysis; atom-based 3D-QSAR