1,3,4-恶二唑作为治疗阿尔茨海默病潜在先导化合物的治疗潜力
Therapeutic potential of 1,3,4-oxadiazoles as potential lead compounds for the treatment of Alzheimer's disease.
作者信息
Naseem Saira, Temirak Ahmed, Imran Aqeel, Jalil Saquib, Fatima Shamool, Taslimi Parham, Iqbal Jamshed, Tasleem Mussarat, Tahir Muhammad Nawaz, Shafiq Zahid
机构信息
Institute of Chemical Sciences, Bahauddin Zakariya University Multan 60800 Pakistan
National Research Centre, Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute Dokki, Cairo P.O. Box 12622 Egypt.
出版信息
RSC Adv. 2023 Jun 9;13(26):17526-17535. doi: 10.1039/d3ra01953e.
Monoamine oxidase and cholinesterase enzymes are important targets for the treatment of several neurological diseases especially depression, Parkinson disease and Alzheimer's. Here, we report the synthesis and testing of new 1,3,4-oxadiazole derivatives as novel inhibitors of monoamine oxidase enzymes (MAO-A and MAO-B) and cholinesterase enzymes (acetyl and butyryl cholinesterase (AChE, BChE). Compounds 4c, 4d, 4e, 4g, 4j, 4k, 4m, 4n displayed promising inhibitory effects on MAO-A (IC: 0.11-3.46 μM), MAO-B (IC: 0.80-3.08 μM) and AChE (IC: 0.83-2.67 μM). Interestingly, compounds 4d, 4e and 4g are multitargeting MAO-A/B and AChE inhibitors. Also, Compound 4m displayed promising MAO-A inhibition with IC of 0.11 μM and high selectivity (∼25-fold) over MAO-B and AChE enzymes. These newly synthesized analogues represent promising hits for the development of promising lead compounds for neurological disease treatment.
单胺氧化酶和胆碱酯酶是治疗多种神经疾病尤其是抑郁症、帕金森病和阿尔茨海默病的重要靶点。在此，我们报告了新型1,3,4-恶二唑衍生物的合成与测试，这些衍生物是单胺氧化酶（MAO-A和MAO-B）和胆碱酯酶（乙酰胆碱酯酶和丁酰胆碱酯酶（AChE、BChE））的新型抑制剂。化合物4c、4d、4e、4g、4j、4k、4m、4n对MAO-A（IC：0.11 - 3.46 μM）、MAO-B（IC：0.80 - 3.08 μM）和AChE（IC：0.83 - 2.67 μM）显示出有前景的抑制作用。有趣的是，化合物4d、4e和4g是多靶点MAO-A/B和AChE抑制剂。此外，化合物4m对MAO-A显示出有前景的抑制作用，IC为0.11 μM，并且对MAO-B和AChE酶具有高选择性（约25倍）。这些新合成的类似物代表了开发用于治疗神经疾病的有前景先导化合物的有前景的起始化合物。
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