title: First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!
abstract: Huntington's disease (HD) is caused by mutation of huntingtin protein (mHtt) leading to neuronal cell death. The mHtt induced toxicity can be rescued by inhibiting the kynurenine monooxygenase (KMO) enzyme. Therefore, KMO is a promising drug target to address the neurodegenerative disorders such as Huntington's diseases. Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches. Moreover, ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts.
authors.affiliation: Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, Madhya Pradesh, India; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, PO Box 17020, Jadavpur University, Kolkata 700032, West Bengal, India.
authors.forename: Sk Abdul
authors.initials: SA
authors.lastname: Amin
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, PO Box 17020, Jadavpur University, Kolkata 700032, West Bengal, India.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Adhikari
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, PO Box 17020, Jadavpur University, Kolkata 700032, West Bengal, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
authors.affiliation: Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, Madhya Pradesh, India.
authors.forename: Shovanlal
authors.initials: S
authors.lastname: Gayen
mesh_terms: D001499:Bayes Theorem; D016002:Discriminant Analysis; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D016571:Neural Networks, Computer; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D050601:Kynurenine 3-Monooxygenase
keywords: Artificial neural network; Bayesian modeling; Huntington’s disease; Kynurenine monooxygenase; Linear discriminant analysis; Molecular docking; Pharmacophore mapping; Support vector machine