Skip to Main content Skip to Navigation
New interface
Journal articles

Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans

Abstract : We investigated the antifungal activity of fused Mannich ketone (FMK) congeners and two of their aminoalcohol derivatives. In particular, FMKs with five-membered saturated rings were shown to have minimum inhibitory concentration (MIC90s) ranging from 0.8 to 6 µg/mL toward C. albicans and the closely related C. parapsilosis and C. krusei while having reduced efficacy toward C. glabrata and almost no efficacy against Aspergillus sp. Transcript profiling of C. albicans cells exposed for 30 or 60 min to 2-(morpholinomethyl)-1-indanone, a representative FMK with a five-membered saturated ring, revealed a transcriptional response typical of oxidative stress and similar to that of a C. albicans Cap1 transcriptional activator. Consistently, C. albicans lacking the CAP1 gene was hypersensitive to this FMK, while C. albicans strains overexpressing CAP1 had decreased sensitivity to 2-(morpholinomethyl)-1-indanone. Quantitative structure-activity relationship studies revealed a correlation of antifungal potency and the energy of the lowest unoccupied molecular orbital of FMKs and unsaturated Mannich ketones thereby implicating redox cycling-mediated oxidative stress as a mechanism of action. This conclusion was further supported by the loss of antifungal activity upon conversion of representative FMKs to aminoalcohols that were unable to participate in redox cycles.
Document type :
Journal articles
Complete list of metadata

Cited literature [61 references]  Display  Hide  Download
Contributor : christelle lenormand Connect in order to contact the contributor
Submitted on : Monday, May 15, 2017 - 4:42:40 PM
Last modification on : Thursday, April 7, 2022 - 10:10:23 AM
Long-term archiving on: : Thursday, August 17, 2017 - 12:14:55 AM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




Tristan Rossignol, Béla Kocsis, Orsolya Bouquet, Ildikó Kustos, Ferenc Kilár, et al.. Antifungal Activity of Fused Mannich Ketones Triggers an Oxidative Stress Response and Is Cap1-Dependent in Candida albicans. PLoS ONE, 2013, 8 (4), pp.e62142. ⟨10.1371/journal.pone.0062142⟩. ⟨pasteur-01522885⟩



Record views


Files downloads