Synthesis and biological evaluation of pyrano[4,3-b][1]benzopyranone derivatives as monoamine oxidase and cholinesterase inhibitors |
| |
| Institution: | 1. Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China;2. College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;3. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Institute of Biomedicine and Biotechnology, Shenzhen, Guangdong 518055, China;4. State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, China;5. Xiangxue Academician Workstation, Xiangxue Pharmaceutical Co. Ltd, Guangzhou 510663, China;1. Department of Chemistry, Government College University, Faisalabad 38000, Pakistan;2. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan;3. Department of Chemistry, Government College Women University, Faisalabad 38000, Pakistan;4. Department of Zoology, Government College University, Faisalabad 38000, Pakistan;5. Chemistry Department, Faculty of Science, King Abdulaziz University, P. O. Box 80203, Jeddah 21589, Saudi Arabia;6. Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P. O. Box 80203, Jeddah 21589, Saudi Arabia;7. Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;8. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;9. HEJ Research Institute of Chemistry, University of Karachi, Karachi, Pakistan |
| |
| Abstract: | A series of eighteen pyrano4,3-b]1]benzopyranone derivatives (1a-9b) were synthesized, and structure-activity relationships of their monoamine oxidase (MAO) A and B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities were evaluated. Most of the synthesized compounds exhibited weak inhibitory activity toward MAO-A, whereas compounds 2a, 2b, 4a, 4b, 5a, 5b, 6a, 6b, 8a and 8b showed potent inhibitory activities toward MAO-B. Intriguingly, compounds 5a, 5b, and 8a showed inhibitory activities comparable to pargylin, used as a positive control for MAO-B. Substitution of butoxy at the C3 position or of chlorine at the C8 position of pyrano4,3-b]1]benzopyranone increased the inhibitory activity of the compound toward MAO-B. The results of a molecular docking study supported this structural effect. Most of the compounds exhibited no or slight inhibitory activity toward AChE and BChE, with exo type compounds bearing a butoxy group, such as compounds 2b, 5b and 8b, showing weak but distinct inhibitory activities toward BChE. This report is the first to identify pyrano4,3-b]1]benzopyranone derivatives as potent and selective MAO-B inhibitors. 3-Butoxy-8-chloro-pyrano4,3-b]1]benzopyranone (5b) may be useful as a lead compound for the development of MAO-B inhibitors. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
