Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction
An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-<i>b</i>]quinaz...
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2025-06-01
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| author | Davron Turgunov Lifei Nie Azizbek Nasrullaev Zarifa Murtazaeva Bianlin Wang Dilafruz Kholmurodova Rustamkhon Kuryazov Jiangyu Zhao Khurshed Bozorov Haji Akber Aisa |
| author_facet | Davron Turgunov Lifei Nie Azizbek Nasrullaev Zarifa Murtazaeva Bianlin Wang Dilafruz Kholmurodova Rustamkhon Kuryazov Jiangyu Zhao Khurshed Bozorov Haji Akber Aisa |
| author_sort | Davron Turgunov |
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| description | An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-<i>b</i>]quinazolin-9(1<i>H</i>)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-<i>b</i>]quinazolin-9(1<i>H</i>)-one derivative exhibited the highest inhibitory potency, with an IC<sub>50</sub> value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease. |
| format | Article |
| id | doaj-art-75786a4eeeac448cb848e2a613a8b1f4 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-75786a4eeeac448cb848e2a613a8b1f42025-08-20T03:28:33ZengMDPI AGMolecules1420-30492025-06-013013279110.3390/molecules30132791Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling ReactionDavron Turgunov0Lifei Nie1Azizbek Nasrullaev2Zarifa Murtazaeva3Bianlin Wang4Dilafruz Kholmurodova5Rustamkhon Kuryazov6Jiangyu Zhao7Khurshed Bozorov8Haji Akber Aisa9Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanState Key Laboratory Basis of Xinjiang Indigenous Míicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, ChinaDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanState Key Laboratory Basis of Xinjiang Indigenous Míicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, ChinaScientific and Practical Center of Immunology, Allergology and Human Genomics, Samarkand State Medical University, Makhdum-i Aʿẓam st. 18, Samarkand 140104, UzbekistanDepartment of Chemistry, Urgench State University, Kh. Olimjon st. 14, Urgench 220100, UzbekistanState Key Laboratory Basis of Xinjiang Indigenous Míicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, ChinaDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanState Key Laboratory Basis of Xinjiang Indigenous Míicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, ChinaAn important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-<i>b</i>]quinazolin-9(1<i>H</i>)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-<i>b</i>]quinazolin-9(1<i>H</i>)-one derivative exhibited the highest inhibitory potency, with an IC<sub>50</sub> value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease.https://www.mdpi.com/1420-3049/30/13/2791Acetylcholinesterase (AChE)Alzheimer’s diseaseButyrylcholinesterase (BChE)carbon–carbon bond (C-C)deoxyvasicinonemackinazolinone |
| spellingShingle | Davron Turgunov Lifei Nie Azizbek Nasrullaev Zarifa Murtazaeva Bianlin Wang Dilafruz Kholmurodova Rustamkhon Kuryazov Jiangyu Zhao Khurshed Bozorov Haji Akber Aisa Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction Molecules Acetylcholinesterase (AChE) Alzheimer’s disease Butyrylcholinesterase (BChE) carbon–carbon bond (C-C) deoxyvasicinone mackinazolinone |
| title | Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction |
| title_full | Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction |
| title_fullStr | Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction |
| title_full_unstemmed | Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction |
| title_short | Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-<i>b</i>]Quinazolin-9(1<i>H</i>)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction |
| title_sort | synthesis of novel 7 phenyl 2 3 dihydropyrrolo 2 1 i b i quinazolin 9 1 i h i ones as cholinesterase inhibitors targeting alzheimer s disease through suzuki miyaura cross coupling reaction |
| topic | Acetylcholinesterase (AChE) Alzheimer’s disease Butyrylcholinesterase (BChE) carbon–carbon bond (C-C) deoxyvasicinone mackinazolinone |
| url | https://www.mdpi.com/1420-3049/30/13/2791 |
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