Novel 12-hydroxydehydroabietylamine derivatives act as potent and selective butyrylcholinesterase inhibitors |
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| Affiliation: | 1. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Leibniz Institute of Plant Biochemistry, Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany;1. Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil;2. Department of Chemistry, Universidade Federal de Viçosa, CEP 36570-900, Viçosa, MG, Brazil;3. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120, Halle (Saale), Germany;1. Department of Biological and Ecological Sciences, University of Tuscia, Largo dell’Università, Viterbo 01100, Italy;2. Università degli Studi della Campania Luigi Vanvitelli, Dipartimento di Medicina di Precisione Vico L. De Crecchio 7, 80138 Napoli, Italy;1. Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies, Sultan Moulay Slimane University, BP 523, 23000 Beni-Mellal, Morocco;2. Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, via E. Orabona, 4, 70125 Bari, Italy;1. Department of Psychiatry and Behavioral Sciences, Sylvester Comprehensive Cancer Center, and Center for Therapeutic Innovation, University of Miami, Miami, FL 33136, USA;2. Department of Neurological Surgery, Miami Project to Cure Paralysis, and Center for Therapeutic Innovation, University of Miami, Miami, FL 33136, USA;3. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA;4. Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, and Center for Therapeutic Innovation, University of Miami, Miami, FL 33136, USA;1. Institute of Medicinal Chemistry and Biology, College of Pharmacy, Jinan University, Guangzhou, China;2. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;3. School of Life Sciences, University of Science and Technology of China, Hefei 230026, China;4. Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China |
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| Abstract: | The skeleton of the diterpene dehydroabietylamine was modified, and a set of 12-hydroxy-dehydroabietylamine derivatives was obtained. The compounds were screened in colorimetric Ellman’s assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). Additional investigations concerning the enzyme kinetics were performed and showed 12-hydroxy-N-(4-nitro-benzoyl)dehydroabietylamine (13) and 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine (17) as selective BChE inhibitors holding good inhibition constants Ki = 0.72 ± 0.06 μM and Ki = 0.86 ± 0.19 μM, respectively. |
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