6EZH
Torpedo californica AChE in complex with indolic multi-target directed ligand
Summary for 6EZH
| Entry DOI | 10.2210/pdb6ezh/pdb |
| Related | 1ea5 1eve 2w75 6ezg |
| Descriptor | Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1-(7-chloranyl-4-methoxy-1~{H}-indol-5-yl)-3-[1-(cyclohexylmethyl)piperidin-4-yl]propan-1-one, ... (4 entities in total) |
| Functional Keywords | acetylcholinesterase, multi-target inhibitor, alzheimer desease, hydrolase |
| Biological source | Tetronarce californica (Pacific electric ray) |
| Total number of polymer chains | 2 |
| Total formula weight | 123191.83 |
| Authors | Santoni, G.,Lalut, J.,Karila, D.,Lecoutey, C.,Davis, A.,Nachon, F.,Sillman, I.,Sussman, J.,Weik, M.,Maurice, T.,Dallemagne, P.,Rochais, C. (deposition date: 2017-11-15, release date: 2018-11-21, Last modification date: 2024-11-13) |
| Primary citation | Lalut, J.,Santoni, G.,Karila, D.,Lecoutey, C.,Davis, A.,Nachon, F.,Silman, I.,Sussman, J.,Weik, M.,Maurice, T.,Dallemagne, P.,Rochais, C. Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase. Eur J Med Chem, 162:234-248, 2018 Cited by PubMed Abstract: Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the σ receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition. PubMed: 30447434DOI: 10.1016/j.ejmech.2018.10.064 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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