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Whereas different ruthenium complexes were previously studied for their anti\u2010<jats:italic>Candida<\/jats:italic> potential, Ru\u2010cyclopentadienyl complexes were overlooked. Here, we report an antifungal activity assessment of three Ru\u2010cyclopentadienyl complexes with some insights into their potential mode of action. Among these complexes, only the cationic species [Ru\u2010ACN]<jats:sup>+<\/jats:sup> and [Ru\u2010ATZ]<jats:sup>+<\/jats:sup> displayed a significant antifungal activity against different <jats:italic>Candida<\/jats:italic> strains, notably against the ones that did not respond to one of the most currently used antifungal drugs fluconazole (FCZ). However, no apparent activity was observed for the neutral species, Ru\u2212Cl, thus indicating the important role of the cationic backbone of these complexes in their biological activity. We suggest that reactive oxygen species (ROS) generation might be involved in the mechanism of action of these complexes as, unlike neutral Ru\u2212Cl, [Ru\u2010ACN]<jats:sup>+<\/jats:sup> and [Ru\u2010ATZ]<jats:sup>+<\/jats:sup> could generate intracellular concentration\u2010dependent ROS. We also observed a correlation between the ruthenium cellular uptake, ROS generation and fungal growth inhibitory activity of the compounds. Furthermore, docking simulations showed that the CYP51 enzyme can form more energetically favorable complexes with [Ru\u2010ATZ]<jats:sup>+<\/jats:sup> than fluconazole (FCZ); this suggests that CYP51 inhibition could also be considered as a potential mode of action.<\/jats:p>","DOI":"10.1002\/cbic.202000254","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:17:30Z","timestamp":1592957850000},"page":"3112-3119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cationic Ru<sup>II<\/sup> Cyclopentadienyl Complexes with Antifungal Activity against Several <i>Candida<\/i> Species"],"prefix":"10.1002","volume":"21","author":[{"given":"Golara","family":"Golbaghi","sequence":"first","affiliation":[{"name":"Organometallic Chemistry Laboratory for the Design of Catalysts and Therapeutics INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie  531 boul. des Prairies Laval, Quebec H7V 1B7 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