Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue
Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder, characterized by β-amyloid plaques, neurofibrillary tangles and loss of cholinergic neurons. Butyrylcholinesterase (BChE) inhibition is one of the most critical strategy for the treatment of AD since BChE causes...
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| Format: | Article |
| Language: | English |
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Turkish Chemical Society
2021-05-01
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| Series: | Journal of the Turkish Chemical Society, Section A: Chemistry |
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| Online Access: | https://dergipark.org.tr/tr/pub/jotcsa/issue/60129/853598 |
| _version_ | 1797922862896513024 |
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| author | Kevser BIBEROGLU |
| author_facet | Kevser BIBEROGLU |
| author_sort | Kevser BIBEROGLU |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder, characterized by β-amyloid plaques, neurofibrillary tangles and loss of cholinergic neurons. Butyrylcholinesterase (BChE) inhibition is one of the most critical strategy for the treatment of AD since BChE causes inactivation of neurotransmitter acetylcholine and has positive effects on promoting the formation of β-amyloid fibrils. Our previous studies showed that various phenothiazine-derived compounds such as thionine and toluidine blue O (TBO) cause a potent inhibition of human cholinesterases. TBO was also found to reduce amyloid precursor protein processing in-vitro and in-vivo models of AD. In this study, it was aimed to determine the inhibitory effect of 1,9-dimethyl-methylene blue (DMMB), a phenothiazine-derived compound, on human plasma BChE and explore its inhibitory mechanism. The inhibition of human BChE was assessed by the colorimetric method of Ellman using butyrylthiocholine as substrate and 0-0.375 μM of DMMB. The kinetic findings showed that DMMB acts as a linear mixed-type inhibitor of human BChE with Ki value of 23 ± 0.004 nM and α= 3.6 ± 1.6. It was concluded that DMMB, which is a potent inhibitor effective at nM level may be helpful in designing new cholinesterase inhibitors for the treatment of AD. |
| first_indexed | 2024-04-10T14:37:54Z |
| format | Article |
| id | doaj.art-18b2e12bb6a548499a21e0433088aef2 |
| institution | Directory Open Access Journal |
| issn | 2149-0120 |
| language | English |
| last_indexed | 2024-04-10T14:37:54Z |
| publishDate | 2021-05-01 |
| publisher | Turkish Chemical Society |
| record_format | Article |
| series | Journal of the Turkish Chemical Society, Section A: Chemistry |
| spelling | doaj.art-18b2e12bb6a548499a21e0433088aef22023-02-15T16:08:21ZengTurkish Chemical SocietyJournal of the Turkish Chemical Society, Section A: Chemistry2149-01202021-05-018243544210.18596/jotcsa.853598Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blueKevser BIBEROGLU0https://orcid.org/0000-0001-9285-0819HACETTEPE UNIVERSITY, FACULTY OF PHARMACYAlzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder, characterized by β-amyloid plaques, neurofibrillary tangles and loss of cholinergic neurons. Butyrylcholinesterase (BChE) inhibition is one of the most critical strategy for the treatment of AD since BChE causes inactivation of neurotransmitter acetylcholine and has positive effects on promoting the formation of β-amyloid fibrils. Our previous studies showed that various phenothiazine-derived compounds such as thionine and toluidine blue O (TBO) cause a potent inhibition of human cholinesterases. TBO was also found to reduce amyloid precursor protein processing in-vitro and in-vivo models of AD. In this study, it was aimed to determine the inhibitory effect of 1,9-dimethyl-methylene blue (DMMB), a phenothiazine-derived compound, on human plasma BChE and explore its inhibitory mechanism. The inhibition of human BChE was assessed by the colorimetric method of Ellman using butyrylthiocholine as substrate and 0-0.375 μM of DMMB. The kinetic findings showed that DMMB acts as a linear mixed-type inhibitor of human BChE with Ki value of 23 ± 0.004 nM and α= 3.6 ± 1.6. It was concluded that DMMB, which is a potent inhibitor effective at nM level may be helpful in designing new cholinesterase inhibitors for the treatment of AD.https://dergipark.org.tr/tr/pub/jotcsa/issue/60129/853598alzheimer’s diseasebutyrylcholinesterase19-dimethyl-methylene bluecholinesterase inhibitionphenothiazine |
| spellingShingle | Kevser BIBEROGLU Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue Journal of the Turkish Chemical Society, Section A: Chemistry alzheimer’s disease butyrylcholinesterase 1 9-dimethyl-methylene blue cholinesterase inhibition phenothiazine |
| title | Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue |
| title_full | Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue |
| title_fullStr | Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue |
| title_full_unstemmed | Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue |
| title_short | Kinetics of human butyrylcholinesterase inhibition by 1,9-dimethyl-methylene blue |
| title_sort | kinetics of human butyrylcholinesterase inhibition by 1 9 dimethyl methylene blue |
| topic | alzheimer’s disease butyrylcholinesterase 1 9-dimethyl-methylene blue cholinesterase inhibition phenothiazine |
| url | https://dergipark.org.tr/tr/pub/jotcsa/issue/60129/853598 |
| work_keys_str_mv | AT kevserbiberoglu kineticsofhumanbutyrylcholinesteraseinhibitionby19dimethylmethyleneblue |