Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors
Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6&...
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2024-11-01
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| author | Sofia I. Presnukhina Valentina D. Kotlyarova Anton A. Shetnev Sergey V. Baykov Rakhymzhan Turmanov Nurbol Appazov Rakhmetulla Zhapparbergenov Leilya Zhussupova Nurila Togyzbayeva Stephanus J. Cloete Mikhail K. Korsakov Vadim P. Boyarskiy Anél Petzer Jacobus P. Petzer |
| author_facet | Sofia I. Presnukhina Valentina D. Kotlyarova Anton A. Shetnev Sergey V. Baykov Rakhymzhan Turmanov Nurbol Appazov Rakhmetulla Zhapparbergenov Leilya Zhussupova Nurila Togyzbayeva Stephanus J. Cloete Mikhail K. Korsakov Vadim P. Boyarskiy Anél Petzer Jacobus P. Petzer |
| author_sort | Sofia I. Presnukhina |
| collection | DOAJ |
| description | Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6<i>H</i>)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6<i>H</i>)-ones. The results of the in vitro MAO inhibition studies showed that the 1,2,4-oxadiazin-5(6<i>H</i>)-ones were indeed inhibitors of human MAO with the most potent inhibition observed for <b>5f</b> (IC<sub>50</sub> = 0.900 µM) and <b>7c</b> (IC<sub>50</sub> = 0.371 µM). It was concluded that, with appropriate substitution, 1,2,4-oxadiazin-5(6<i>H</i>)-one derivatives would act as good potency MAO-B inhibitors and lead compounds for the development of antiparkinsonian drugs. In Parkinson’s disease, MAO-B inhibitors enhance central dopamine levels and reduce MAO-mediated production of hydrogen peroxide and resultant oxidative injury. This study represents one of few works to investigate synthetic approaches and biological activities of the 1,2,4-oxadiazin-5(6<i>H</i>)-one class of heterocycles. |
| format | Article |
| id | doaj-art-666d1696e3a345529b3f8441fd9f2dec |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Molecules |
| spelling | doaj-art-666d1696e3a345529b3f8441fd9f2dec2025-08-20T02:38:45ZengMDPI AGMolecules1420-30492024-11-012923555010.3390/molecules29235550Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase InhibitorsSofia I. Presnukhina0Valentina D. Kotlyarova1Anton A. Shetnev2Sergey V. Baykov3Rakhymzhan Turmanov4Nurbol Appazov5Rakhmetulla Zhapparbergenov6Leilya Zhussupova7Nurila Togyzbayeva8Stephanus J. Cloete9Mikhail K. Korsakov10Vadim P. Boyarskiy11Anél Petzer12Jacobus P. Petzer13Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, 199034 Saint Petersburg, RussiaPharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, Respublikanskaya St., 108, 150000 Yaroslavl, RussiaLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanInstitute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, 199034 Saint Petersburg, RussiaLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanLaboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda 120014, KazakhstanPharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South AfricaPharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, Respublikanskaya St., 108, 150000 Yaroslavl, RussiaInstitute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, 199034 Saint Petersburg, RussiaPharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South AfricaPharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South AfricaMonoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6<i>H</i>)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6<i>H</i>)-ones. The results of the in vitro MAO inhibition studies showed that the 1,2,4-oxadiazin-5(6<i>H</i>)-ones were indeed inhibitors of human MAO with the most potent inhibition observed for <b>5f</b> (IC<sub>50</sub> = 0.900 µM) and <b>7c</b> (IC<sub>50</sub> = 0.371 µM). It was concluded that, with appropriate substitution, 1,2,4-oxadiazin-5(6<i>H</i>)-one derivatives would act as good potency MAO-B inhibitors and lead compounds for the development of antiparkinsonian drugs. In Parkinson’s disease, MAO-B inhibitors enhance central dopamine levels and reduce MAO-mediated production of hydrogen peroxide and resultant oxidative injury. This study represents one of few works to investigate synthetic approaches and biological activities of the 1,2,4-oxadiazin-5(6<i>H</i>)-one class of heterocycles.https://www.mdpi.com/1420-3049/29/23/5550monoamine oxidaseMAOoxadiazineinhibitionParkinson’s disease |
| spellingShingle | Sofia I. Presnukhina Valentina D. Kotlyarova Anton A. Shetnev Sergey V. Baykov Rakhymzhan Turmanov Nurbol Appazov Rakhmetulla Zhapparbergenov Leilya Zhussupova Nurila Togyzbayeva Stephanus J. Cloete Mikhail K. Korsakov Vadim P. Boyarskiy Anél Petzer Jacobus P. Petzer Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors Molecules monoamine oxidase MAO oxadiazine inhibition Parkinson’s disease |
| title | Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors |
| title_full | Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors |
| title_fullStr | Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors |
| title_full_unstemmed | Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors |
| title_short | Synthesis of 1,2,4-Oxadiazin-5(6<i>H</i>)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors |
| title_sort | synthesis of 1 2 4 oxadiazin 5 6 i h i one derivatives and their biological investigation as monoamine oxidase inhibitors |
| topic | monoamine oxidase MAO oxadiazine inhibition Parkinson’s disease |
| url | https://www.mdpi.com/1420-3049/29/23/5550 |
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