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However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB\u2013rimonabant polytherapies for fungal infections.<\/jats:p>","DOI":"10.1093\/femsyr\/foab016","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T07:19:31Z","timestamp":1614669571000},"source":"Crossref","is-referenced-by-count":13,"title":["Rimonabant potentiates the antifungal activity of amphotericin B by increasing cellular oxidative stress and cell membrane permeability"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-6425","authenticated-orcid":false,"given":"Ming","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Natural Product Chemistry, Key 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