Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential |
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| Institution: | 1. Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Universidade de Lisboa, Faculdade de Farmácio, Instituto de Investigacao do Medicamento (iMed.ULisboa), Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal;3. Martin-Luther-University Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Str. 4, D-06120 Halle (Saale), Germany;4. University of Nizwa, Chair of Oman’s Medicinal Plants and Marine Natural Products, PO Box 33, Birkat Al-Mauz, Nizwa, Oman;1. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, E-18071, Granada, Spain;2. Departamento de Bioquímica y Biología Molecular I, Facultad de Ciencias, Universidad de Granada, E-18071, Granada, Spain;1. Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany;2. Instituto de Investigacao do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal;1. Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China;2. Department of Applied Physics, Huzhou University, Huzhou 313000, China;3. Library of Jiangxi Agricultural University, Nanchang 330045, China;4. College of Science, Jiangxi Agricultural University, Nanchang 330045, China;1. Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal;2. Center for Neuroscience and Cell Biology, Coimbra, Portugal;3. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA |
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| Abstract: | Triterpenoids are in the focus of scientific interest, and they were evaluated for many pharmacological applications among them their ability to act as inhibitors of cholinesterases. These inhibitors are still of interest as drugs that improve the life quality of patients suffering from age-related dementia illnesses especially of Alzheimer’s disease. Herein, we prepared several derivatives of ursolic and oleanolic acid and screened them in Ellman’s assays for their ability to inhibit acetylcholinesterase and/or butyrylcholinesterase, and for each of the active compounds the type of inhibition was determined. As a result, several compounds were shown as good inhibitors for acetylcholinesterase and butyrylcholinesterase even in a micromolar range. An ursolic acid derived hydroxyl-propinyl derivative 10 was a competitive inhibitor for butyrylcholinesterase with an inhibition constant of Ki = 4.29 μM, and therefore being twice as active as gold standard galantamine hydrobromide. The best inhibitor for acetylcholinesterase, however, was 2-methyl-3-oxo-methyl-ursoloate (18), acting as a mixed-type inhibitor showing Ki = 1.72 µM and Ki′ = 1.28 μM, respectively. |
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