Selected C7-substituted chromone derivatives as monoamine oxidase inhibitors |
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| Institution: | 1. Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa;2. Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa;1. Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, 678557, Kerala, India;2. Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India;3. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 S?hhiye, Ankara, Turkey;4. School of Pure & Applied Physics, M.G. University, Kottayam, India;5. Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, India;6. Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai 600003, India;1. Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India;2. Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India;3. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 S?hhiye, Ankara, Turkey;4. Department of Pharmaceutical Chemistry, Madras Medical College, Chennai 600004, India;1. Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza – Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy;2. Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur, E-15782, Santiago de Compostela (La Coruña), Spain;3. Dipartimento di Scienze della Salute, Università“Magna Græcia” di Catanzaro, Campus Universitario “S. Venuta”, Viale Europa, 88100, Catanzaro, Italy;1. Laboratory of Bioorganic Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1-1 Keyaki-dai, Sakado, Saitama 350-0295, Japan;2. Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-858, Japan;1. Yaroslavl State Technical University, 150023 Yaroslavl, Russian Federation;2. Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa;3. A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov St., 119991 Moscow, Russian Federation;1. College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, 473061, China;2. Department of Elderly Digestive, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, China;3. Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China;4. Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, China |
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| Abstract: | A series of C7-substituted chromone (1-benzopyran-4-one) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The chromones are structurally related to a series of C7-functionalized coumarin (1-benzopyran-2-one) derivatives which has been reported to act as potent MAO inhibitors. The results of the current study document that the chromones are highly potent reversible inhibitors of MAO-B with IC50 values ranging from 0.008 to 0.370 μM. While the chromone derivatives also exhibit affinities for MAO-A, with IC50 values ranging from 0.495 to 8.03 μM, they are selective for the MAO-B isoform. Structure–activity relationships (SAR) show that 7-benzyloxy substitution of chromone is suitable for MAO-B inhibition with tolerance for a variety of substituents and substitution patterns on the benzyloxy ring. It may be concluded that 7-benzyloxychromones are appropriate lead compounds for the design of reversible and selective MAO-B inhibitors. With the aid of modeling studies, potential binding orientations and interactions of selected chromone derivatives in the MAO-A and -B active sites are examined. |
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