Solvents and detergents compatible with enzyme kinetic studies of cholinesterases.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that serve a wide range of physiological functions including the hydrolysis of the neurotransmitter acetylcholine and several other xenobiotics. The development of inhibitors for these enzymes has been the focus for the treatment of several conditions, such as Alzheimer's disease. Novel chemical entities are evaluated as potential inhibitors of AChE and BChE using enzyme kinetics. A common issue encountered in these studies is low aqueous solubility of the possible inhibitor. Additives such as cosolvents or detergents can be included in these studies improve the aqueous solubility. Typical cosolvents include acetonitrile or dimethyl sulfoxide while typical detergents include Polysorbate 20 (Tween 20) or 3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate (CHAPS). When solubility is not improved, these molecules are often not evaluated further. To address this issue eleven cosolvents and six detergents that could facilitate aqueous solubility were evaluated to understand how they would affect cholinesterase enzymes using Ellman's assay. These studies show that propylene glycol, acetonitrile, methanol, Tween 20, Polysorbate 80 (Tween 80), polyoxyethylene 23 lauryl ether (Brij 35) and polyoxyethylene 10 oleoyl ether (Brij 96v) have the least inhibitory effects towards cholinesterase activity. It is concluded that these cosolvents and detergents should be considered as solubilizing agents for evaluation of potential cholinesterase inhibitors with low aqueous solubility.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sultan Darvesh reports financial support was provided by Canadian Institutes of Health Research. Ian Pottie reports financial support was provided by Canadian Institutes of Health Research. Ian Pottie reports financial support was provided by Canada Foundation for Innovation. Sultan Darvesh reports financial support was provided by Canada Foundation for Innovation. Sultan Darvesh reports financial support was provided by Dalhousie Medical Research Foundation. Sultan Darvesh reports a relationship with Treventis Corporation that includes: equity or stocks and non-financial support. Sultan Darvesh has patent #International Publication Number WO 01/92240 issued to Treventis Corporation. Sultan Darvesh has patent #US Patent #6,436,972 B1 issued to Treventis Corporation. Sultan Darvesh has patent #US Patent #6,544,986 B2 issued to Treventis Corporation. Sultan Darvesh has patent #International Publication Number WO 2010/025368 A1 issued to Treventis Corporation. Ian Pottie has patent #International Publication Number WO 2010/025368 A1 issued to Treventis Corporation. Sultan Darvesh has patent #New Zealand Patent # 591824 issued to Treventis Corporation. Ian Pottie has patent #New Zealand Patent # 591824 issued to Treventis Corporation. Sultan Darvesh has patent #European Patent #2320891 issued to Treventis Corporation. Ian Pottie has patent #European Patent #2320891 issued to Treventis Corporation. Sultan Darvesh has patent #Hong Kong Patent # HK1157227 issued to Treventis Corporation. Ian Pottie has patent #Hong Kong Patent # HK1157227 issued to Treventis Corporation. Sultan Darvesh has patent #International Publication Number WO/2014/039526 issued to Treventis Corporation. Ian Pottie has patent #International Publication Number WO/2014/039526 issued to Treventis Corporation. Sultan Darvesh has patent #US Patent # 8,795,630 issued to Treventis Corporation. Ian Pottie has patent #US Patent # 8,795,630 issued to Treventis Corporation. Sultan Darvesh has patent #Japanese Patent # 5734853 issued to Treventis Corporation. Ian Pottie has patent #Japanese Patent # 5734853 issued to Treventis Corporation. Sultan Darvesh has patent #Australian Patent # 2009285584 issued to Treventis Corporation. Ian Pottie has patent #Australian Patent # 2009285584 issued to Treventis Corporation. Sultan Darvesh has patent #Canadian Patent # 2,735,118 issued to Treventis Corporation. Ian Pottie has patent #Canadian Patent # 2,735,118 issued to Treventis Corporation. Sultan Darvesh has patent #Israeli Patent Application # 211347 issued to Treventis Corporation. Ian Pottie has patent #Israeli Patent Application # 211347 issued to Treventis Corporation. Sultan Darvesh has patent #International Publication Number. WO 2021/026429 A1 issued to Treventis Corporation. Scott Banfield has patent #International Publication Number WO201515131021 A2 issued to Treventis Corporation. Scott Banfield has patent #International Publication Number WO2014031873 A2 issued to Treventis Corporation. Scott Banfield has patent #International Publication Number WO2012119035 A1 issued to Treventis Corporation. Sultan Darvesh has patent #Chinese Patent Application 200980137701.7 pending to Treventis Corporation. Ian Pottie has patent #Chinese Patent Application 200980137701.7 pending to Treventis Corporation. Sultan Darvesh has patent #US Provisional patent application Serial No. 61/736,146 pending to Treventis Corporation. Corresponding Author is an Associate Editor of Current Alzheimer Research - S.D.