Design,synthesis, in silico and in vitro screening of 1,2,4-thiadiazole analogues as non-peptide inhibitors of beta-secretase |
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| Institution: | 1. Prin. K.M. Kundnani College of Pharmacy, 23 Jote Joy, R.S. Marg, Cuffe Parade, Mumbai 400 005, India;2. Department for Life Quality Studies, Rimni Campus, University of Bologna, Italy;1. Vrije Universiteit Brussel, Department of Chemical Engineering (CHIS-IR), Pleinlaan 2, 1050 Brussels, Belgium;2. Thermo Scientific, Manor Park, Tudor Road, Runcorn, GB, UK;1. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Science, S. Kovalevskoi St., 22, Ekaterinburg, 620108, Russia;2. Ural Federal University Named After the First President of Russia B.N. Yeltsin, Mira St. 19, Ekaterinburg, 620002, Russia;3. Perm National Research Polytechnic University, Komsomolsky Av., 29, Perm, 614990, Russia;4. Ural Research Institute for Dermatology, Venereology and Immunopathology, Shcherbakova St., 8, Ekaterinburg, 620076, Russia;5. Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Severny Proezd 1, Chernogolovka, 142432, Russia;6. Ufa Institute of Chemistry of Russian Academy of Science, Octyabrya Av., 71, Ufa, 450078, Russia;1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, Jiangsu, PR China;1. Department of Chemical Sciences, University of Naples “Federico II”, Via Cintia 4, I-80126 Naples, Italy;2. Caviar Biotec, 563-565 Battersea Park Road, London SW11 3BL, United Kingdom;3. Department of Biochemical Engineering, University College London, Bernard Katz Building, London WC1H 6BT, United Kingdom;1. Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, PR China;2. Department of Chemistry, Sri Jayachamarajendra College of Engineering, Mysuru 570006, Karnataka, India |
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| 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. |
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| Keywords: | Beta-secretase 1 2 4-Thiadiazoles Molecular docking |
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