Reversal of fluconazole resistance in multidrug efflux-resistant fungi by the Dysidea arenaria sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate.
The sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate (ECTA) (1) is the first marine natural product to reverse fluconazole resistance mediated by a Candida albicans MDR efflux pump. The IC(50) of fluconazole is decreased from 300 to 8.5 microM (35-fold enhancement) when combined with 1(3.8 microM). A revised C-6 configuration of 1 is established.
Jacob
Melissa R
MR
National Center for Natural Products Research, Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.
Hossain
Chowdhury Faiz
CF
Mohammed
Kaleem A
KA
Smillie
Troy J
TJ
Clark
Alice M
AM
Walker
Larry A
LA
Nagle
Dale G
DG
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D002782:Cholestenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011161:Porifera / Q000737:chemistry*
C482824:9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate; D000970:Antineoplastic Agents; D002782:Cholestenes; D000666:Amphotericin B; D015725:Fluconazole