title: Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis.
abstract: This article describes discovery of a novel and new class of cholinesterase inhibitors as potential therapeutics for Alzheimer's disease. A series of novel isoalloxazine derivatives were synthesized and biologically evaluated for their potential inhibitory outcome for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds exhibited high activity against both the enzymes AChE as well as BuChE. Of the synthesized compounds, the most potent isoalloxazine derivatives (7m and 7q) showed IC50 values of 4.72 μM and 5.22 μM respectively against AChE; and, 6.98 μM and 5.29 μM respectively against BuChE. These two compounds were further evaluated for their anti-aggregatory activity for β-amyloid (Aβ) in presence and absence of AChE by performing Thioflavin-T (ThT) assay and Congo red (CR) binding assay. In order to evaluate cytotoxic profile of these two potential compounds, cell viability assay of SH-SY5Y human neuroblastoma cells was performed. Further, to understand the binding behavior of these two compounds with AChE and BuChE enzymes, docking studies have been reported.
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kanhed
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Anshuman
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Jatin
authors.initials: J
authors.lastname: Machhi
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Zalak S
authors.initials: ZS
authors.lastname: Parikh
authors.affiliation: Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Pillai
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India. Electronic address: mryadav11@yahoo.co.in.
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D005415:Flavins / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D005415:Flavins; C008173:isoalloxazine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Alzheimer’s disease; Cholinesterase’s inhibition; Cytotoxicity; Isoalloxazine; β-Amyloid