Design, synthesis, in vitro evaluation of a new pyrrolo[1,2‐<i>a</i>]thiazolo[5,4‐<i>d</i>]pyrimidinone derivatives as cholinesterase inhibitors against Alzheimer's disease
Yan ZengState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaLifei NieState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaLiu LiuState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaChao NiuState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaYi LiState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaKhurshed BozorovFaculty of Chemistry Samarkand State University Samarkand UzbekistanJiangyu ZhaoState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences Urumqi ChinaJingshan ShenShanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaHaji Akber AisaUniversity of Chinese Academy of Sciences Beijing China
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Abstract A novel of 40 pyrrolo[1,2‐ a ]thiazolo[5,4‐ d ]pyrimidinone derivatives were designed and synthesized as cholinesterase inhibitor agents. The in vitro enzyme assays proved that most of the compounds effectively inhibited cholinesterases in the micromolar range with little cytotoxicity. Compound G15 exhibited the best inhibitory activity against acetylcholinesterase with an IC 50 of 2.69 ± 0.17 μM. Kinetic analysis and molecular modeling testified the competitive inhibition manner of G15 was more likely to bind to the active center of acetylcholinesterase. Thus, compound G15 can be considered as promising lead compounds or candidates for the development of novel drugs against Alzheimer's disease.
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