Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity
Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-m...
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MDPI AG
2022-09-01
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| author | Alexander A. Titov Rosa Purgatorio Arina Y. Obydennik Anna V. Listratova Tatiana N. Borisova Modesto de Candia Marco Catto Cosimo D. Altomare Alexey V. Varlamov Leonid G. Voskressensky |
| author_facet | Alexander A. Titov Rosa Purgatorio Arina Y. Obydennik Anna V. Listratova Tatiana N. Borisova Modesto de Candia Marco Catto Cosimo D. Altomare Alexey V. Varlamov Leonid G. Voskressensky |
| author_sort | Alexander A. Titov |
| collection | DOAJ |
| description | Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, <b>3e</b> (R<sup>3</sup> = CH<sub>2</sub>OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (<i>K</i><sub>i</sub> = 4.9 μM), equipotent with the corresponding 6-phenyl derivative <b>3n</b> (R<sup>3</sup> = Ph, <i>K</i><sub>i</sub> = 4.5 μM), but 90-fold more water-soluble. |
| first_indexed | 2024-03-09T21:25:53Z |
| format | Article |
| id | doaj.art-9eb6beb5b79e444681424424fdc41cae |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:25:53Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9eb6beb5b79e444681424424fdc41cae2023-11-23T21:08:39ZengMDPI AGMolecules1420-30492022-09-012719627610.3390/molecules27196276Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase ActivityAlexander A. Titov0Rosa Purgatorio1Arina Y. Obydennik2Anna V. Listratova3Tatiana N. Borisova4Modesto de Candia5Marco Catto6Cosimo D. Altomare7Alexey V. Varlamov8Leonid G. Voskressensky9Organic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaDepartment of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, ItalyOrganic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaOrganic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaOrganic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaDepartment of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, ItalyDepartment of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, ItalyDepartment of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, ItalyOrganic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaOrganic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow 117198, RussiaTransformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, <b>3e</b> (R<sup>3</sup> = CH<sub>2</sub>OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (<i>K</i><sub>i</sub> = 4.9 μM), equipotent with the corresponding 6-phenyl derivative <b>3n</b> (R<sup>3</sup> = Ph, <i>K</i><sub>i</sub> = 4.5 μM), but 90-fold more water-soluble.https://www.mdpi.com/1420-3049/27/19/6276acetylcholinesterasebutyrylcholinesterasemonoamine oxidase A and B screeninganti-cholinesterase activityazacyclic allenes3-benzazecines |
| spellingShingle | Alexander A. Titov Rosa Purgatorio Arina Y. Obydennik Anna V. Listratova Tatiana N. Borisova Modesto de Candia Marco Catto Cosimo D. Altomare Alexey V. Varlamov Leonid G. Voskressensky Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity Molecules acetylcholinesterase butyrylcholinesterase monoamine oxidase A and B screening anti-cholinesterase activity azacyclic allenes 3-benzazecines |
| title | Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity |
| title_full | Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity |
| title_fullStr | Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity |
| title_full_unstemmed | Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity |
| title_short | Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity |
| title_sort | synthesis of isomeric 3 benzazecines decorated with endocyclic allene moiety and exocyclic conjugated double bond and evaluation of their anticholinesterase activity |
| topic | acetylcholinesterase butyrylcholinesterase monoamine oxidase A and B screening anti-cholinesterase activity azacyclic allenes 3-benzazecines |
| url | https://www.mdpi.com/1420-3049/27/19/6276 |
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