title: Design, synthesis, in silico and in vitro screening of 1,2,4-thiadiazole analogues as non-peptide inhibitors of beta-secretase.
abstract: Beta-secretase is the key enzyme involved in Alzheimer's disease thus; inhibition of the enzyme can lead to a potential anti-Alzheimer drug. In the search of an effective lead candidate, we have designed non-peptide inhibitor molecules based on amino aromatic heterocyclic motifs specifically, substituted 1,2,4-thiadiazole analogues. In silico modelling was employed to study interaction of the designed ligands in the enzyme active site using molecular docking approach as well as for Absorption, Distribution, Metabolism and Excretion studies. The synthesized analogues were pharmacologically screened using in vitro FRET technique. Overall results indicate that one of the analogues, compound 8 is the most promising one against beta secretase.
authors.affiliation: Prin. K.M. Kundnani College of Pharmacy, 23 Jote Joy, R.S. Marg, Cuffe Parade, Mumbai 400 005, India.
authors.forename: Archana S
authors.initials: AS
authors.lastname: Gurjar
authors.affiliation: Department for Life Quality Studies, Rimni Campus, University of Bologna, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Andrisano
authors.affiliation: Department for Life Quality Studies, Rimni Campus, University of Bologna, Italy.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Simone
authors.affiliation: Prin. K.M. Kundnani College of Pharmacy, 23 Jote Joy, R.S. Marg, Cuffe Parade, Mumbai 400 005, India. Electronic address: vsvelingkar@gmail.com.
authors.forename: Vinay S
authors.initials: VS
authors.lastname: Velingkar
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D062105:Molecular Docking Simulation; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D013830:Thiadiazoles; D053829:Amyloid Precursor Protein Secretases
keywords: 1,2,4-Thiadiazoles; Beta-secretase; In vitro FRET assay; Molecular docking