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Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-b]Quinazolin-9(1H)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction

Davron TurgunovDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanLifei NieState 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, ChinaAzizbek NasrullaevDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanZarifa MurtazaevaDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanBianlin WangState 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, ChinaDilafruz KholmurodovaScientific and Practical Center of Immunology, Allergology and Human Genomics, Samarkand State Medical University, Makhdum-i Aʿẓam st. 18, Samarkand 140104, UzbekistanRustamkhon KuryazovDepartment of Chemistry, Urgench State University, Kh. Olimjon st. 14, Urgench 220100, UzbekistanJiangyu ZhaoState 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, ChinaKhurshed BozorovDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, UzbekistanHaji Akber AisaState 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, China

Moleculesjournal2025en

ABI

Annotatsiya

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-b]quinazolin-9(1H)-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-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC50 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.

Mavzular

Cholinesterase and Neurodegenerative Diseases Synthesis and biological activity Phenothiazines and Benzothiazines Synthesis and Activities

Identifikatorlar

DOI: 10.3390/molecules30132791

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