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Harmine and harmol are two structurally similar \u03b2\u2010carbolines that occur in many medicinal plants. In this work, we chose harmine and harmol to impede the amyloid fibril formation of human islet amyloid polypeptide (hIAPP) associated with type\u20052 diabetes mellitus (T2DM), by a series of physicochemical and biochemical methods. The results indicate that harmine and harmol effectively prevent peptide fibril formation and alleviate toxic oligomer species. In addition, both small molecules exhibit strong binding affinities with hIAPP mainly through hydrophobic and hydrogen bonding interactions, thus reducing the cytotoxicity induced by hIAPP. Their distinct binding pattern with hIAPP is closely linked to the molecular configuration of the two small molecules, affecting their ability to impede peptide aggregation. The study is of great significance for the application and development of \u03b2\u2010carboline alkaloids against T2DM.<\/jats:p>","DOI":"10.1002\/cbic.202300395","type":"journal-article","created":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T22:54:35Z","timestamp":1690152875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b2\u2010Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet Amyloid Polypeptide"],"prefix":"10.1002","volume":"24","author":[{"given":"Yanan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry Renmin University of China  No.59, Zhong Guan Cun Street Haidian District Beijing 100872 P. R. 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