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Currently, treatment for cryptococcal meningitis is limited and new therapeutic options are needed. Historically, medicinal plants are used to treat infectious and inflammatory skin infections. Tryptanthrin is a natural product commonly found in these plants. In this study, we demonstrated that tryptanthrin had antifungal activity with minimum inhibitory concentration (MIC) of 2\u00a0\u03bcg\/ml against Cryptococcus species and of 8\u00a0\u03bcg\/ml against Trichophyton rubrum. Further analysis demonstrated that tryptanthrin exerted fungistatic and potent antifungal activity at elevated temperature. In addition, tryptanthrin exhibited a synergistic effect with the calcineurin inhibitors FK506 and cyclosporine A against Cryptococcus neoformans. Furthermore, our data showed that tryptanthrin induced cell cycle arrest at the G1\/S phase by regulating the expression of genes encoding cyclins and the SBF\/MBF complex (CLN1, MBS1, PCL1, and WHI5) in C. neoformans. Screening of a C. neoformans mutant library further revealed that tryptanthrin was associated with various transporters and signaling pathways such as the calcium transporter (Pmc1) and protein kinase A signaling pathway. In conclusion, tryptanthrin exerted novel antifungal activity against Cryptococcus species through a mechanism that interferes with the cell cycle and signaling pathways.<\/jats:p>","DOI":"10.1093\/mmy\/myaa074","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T11:10:33Z","timestamp":1596280233000},"page":"545-556","source":"Crossref","is-referenced-by-count":18,"title":["Natural alkaloid tryptanthrin exhibits novel anticryptococcal activity"],"prefix":"10.1093","volume":"59","author":[{"given":"Chi-Jan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Liang","family":"Yang","sequence":"additional","affiliation":[{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1966-470X","authenticated-orcid":false,"given":"Ying-Lien","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"2021060422083822800_bib1","doi-asserted-by":"crossref","first-page":"165rv113","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci Transl 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