7BGC
human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor
Summary for 7BGC
| Entry DOI | 10.2210/pdb7bgc/pdb |
| Related | 1p0i |
| Descriptor | Cholinesterase, SULFATE ION, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | inhibitor, alzheimer, butyrylcholinesterase, tacrine, anacardic acid, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 64038.95 |
| Authors | Nachon, F.,Salerno, A.,Bolognesi, M.L. (deposition date: 2021-01-06, release date: 2021-04-28, Last modification date: 2024-11-13) |
| Primary citation | Rossi, M.,Freschi, M.,de Camargo Nascente, L.,Salerno, A.,de Melo Viana Teixeira, S.,Nachon, F.,Chantegreil, F.,Soukup, O.,Prchal, L.,Malaguti, M.,Bergamini, C.,Bartolini, M.,Angeloni, C.,Hrelia, S.,Soares Romeiro, L.A.,Bolognesi, M.L. Sustainable Drug Discovery of Multi-Target-Directed Ligands for Alzheimer's Disease. J.Med.Chem., 64:4972-4990, 2021 Cited by PubMed Abstract: The multifactorial nature of Alzheimer's disease (AD) is a reason for the lack of effective drugs as well as a basis for the development of "multi-target-directed ligands" (MTDLs). As cases increase in developing countries, there is a need of new drugs that are not only effective but also accessible. With this motivation, we report the first sustainable MTDLs, derived from cashew nutshell liquid (CNSL), an inexpensive food waste with anti-inflammatory properties. We applied a framework combination of functionalized CNSL components and well-established acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) tacrine templates. MTDLs were selected based on hepatic, neuronal, and microglial cell toxicity. Enzymatic studies disclosed potent and selective AChE/BChE inhibitors (, , and ), with subnanomolar activities. The X-ray crystal structure of complexed with BChE allowed rationalizing the observed activity (0.0352 nM). Investigation in BV-2 microglial cells revealed antineuroinflammatory and neuroprotective activities for and (already at 0.01 μM), confirming the design rationale. PubMed: 33829779DOI: 10.1021/acs.jmedchem.1c00048 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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