title: In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.
abstract: With the increasing prevalence of fungal infections coupled with emerging drug resistance, there is an urgent need for new and effective antifungal agents. Here we report the antifungal activities of 19 diverse halogenated quinoline (HQ) small molecules against Candida albicans and Cryptococcus neoformans. Four HQ analogues inhibited C. albicans growth with a minimum inhibitory concentration (MIC) of 100 nM, whilst 16 analogues effectively inhibited C. neoformans at MICs of 50-780 nM. Remarkably, two HQ analogues eradicated mature C. albicans and C. neoformans biofilms [minimum biofilm eradication concentration (MBEC) = 6.25-62.5 µM]. Several active HQs were found to penetrate into fungal cells, whilst one inactive analogue was unable to, suggesting that HQs elicit their antifungal activities through an intracellular mode of action. HQs are a promising class of small molecules that may be useful in future antifungal treatments.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Zuo
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Garrison
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Akash
authors.initials: A
authors.lastname: Basak
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Peilan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA. Electronic address: rhuigens@cop.ufl.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Huigens
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA. Electronic address: yding@cop.ufl.edu.
authors.forename: Yousong
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000502:physiology; D054879:Halogenation; D006801:Humans; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011804:Quinolines; C037219:quinoline
keywords: Antifungal activity; Candida albicans; Cryptococcus neoformans; Fungal biofilm eradication; Halogenated quinoline; Permeability