Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem
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| Names | |
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| Preferred IUPAC name
N,N,N-Trimethyl-3-(trifluoroacetyl)anilinium | |
| Identifiers | |
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3D model (JSmol)
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| ChemSpider | |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C11H13F3NO | |
| Molar mass | 232.226 g·mol−1 |
| Hazards | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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1.6 mg/kg (intraperitoneal, mice) (as iodide salt)[1] |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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TMTFA is an extremely potent acetylcholinesterase inhibitor. As a transition state analog of acetylcholinesterase, TMTFA is able to inhibit acetylcholinesterase at extremely low concentrations (within the femtomolar range), making it one of the most potent acetylcholinesterase inhibitors known.[2][3][4]
Mechanism of action
TMTFA has a reactive ketone group that can covalently bind to the serine residue in the active site of acetylcholinesterase. This is due to the electron-withdrawing trifluoromethyl group on the carbonyl group.[5]
See also
References
- ^ Brodbeck, U.; Schweikert, K.; Gentinetta, R.; Rottenberg, M. (April 1979). "Fluorinated aldehydes and ketones acting as quasi-substrate inhibitors of acetylcholinesterase". Biochimica et Biophysica Acta (BBA) - Enzymology. 567 (2): 357–369. doi:10.1016/0005-2744(79)90122-0. PMID 444532.
- ^ Nair, Haridasan K.; Lee, Keun; Quinn, Daniel M. (November 1993). "m-(N,N,N-Trimethylammonio)trifluoroacetophenone: a femtomolar inhibitor of acetylcholinesterase". Journal of the American Chemical Society. 115 (22): 9939–9941. doi:10.1021/ja00075a009.
- ^ Kua, Jeremy; Zhang, Yingkai; McCammon, J. Andrew (2002). "Studying Enzyme Binding Specificity in Acetylcholinesterase Using a Combined Molecular Dynamics and Multiple Docking Approach". Journal of the American Chemical Society. 124 (28): 8260–8267. doi:10.1021/ja020429l. PMID 12105904.
- ^ Butini, Stefania; Campiani, Giuseppe; Borriello, Marianna; Gemma, Sandra; Panico, Alessandro; Persico, Marco; Catalanotti, Bruno; Ros, Sindu; Brindisi, Margherita; Agnusdei, Marianna; Fiorini, Isabella; Nacci, Vito; Novellino, Ettore; Belinskaya, Tatyana; Saxena, Ashima; Fattorusso, Caterina (2008). "Exploiting Protein Fluctuations at the Active-Site Gorge of Human Cholinesterases: Further Optimization of the Design Strategy to Develop Extremely Potent Inhibitors". Journal of Medicinal Chemistry. 51 (11): 3154–3170. doi:10.1021/jm701253t. PMID 18479118.
- ^ Harel, Michal; Quinn, Daniel M.; Nair, Haridasan K.; Silman, Israel; Sussman, Joel L. (January 1996). "The X-ray Structure of a Transition State Analog Complex Reveals the Molecular Origins of the Catalytic Power and Substrate Specificity of Acetylcholinesterase". Journal of the American Chemical Society. 118 (10): 2340–2346. doi:10.1021/ja952232h.
