Biologically active fluorescent farnesol analogs.
We describe ten polyene analogs of farnesol, typified by 3,7,11-trimethyl-2,4,6,8,10-dodecapentenaldehyde oxime, which preserve the length, cross-section, and approximate hydrophobicity of farnesol. Four of the ten display strong quorum-sensing activity in the human pathogen Candida albicans, with IC(50) values for inhibition of germ-tube formation as low as 10 microM. The polyenes display absorption maxima between 320 and 380 nm, with the extinction coefficients for the oximes approaching 100,000. All but two of the analogs are fluorescent, with excitation maxima varying over the range of 320-370 nm. Oxime anti-4, which can undergo fluorescence excitation at wavelengths beyond 400 nm, is demonstrated to be useful for confocal fluorescence microscopic imaging of fungal cells. The farnesol analogs are also expected to be useful for detection of farnesol binding proteins and in determination of farnesol pharmacokinetics.
Department of Chemistry, University of Nebraska, Lincoln, NE 68588, USA.
Roman
R
Shchepin
Raluca
R
Dumitru
Kenneth W
KW
Nickerson
Miranda
M
Lund
Patrick H
PH
Dussault
D002176:Candida albicans / Q000187:drug effects; D005204:Farnesol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010091:Oximes / Q000032:analysis / Q000737:chemistry
D005456:Fluorescent Dyes; D010091:Oximes; D005204:Farnesol