T. Woyke et al., In vitro activities and postantifungal effects of the potent dolastatin 10derivative auristatin PHE, ANTIM AG CH, 45(12), 2001, pp. 3580-3584
The pentapeptide dolavaline-valine-dolaisoleuine-dolaproine-phenylalanine-m
ethyl ester (auristatin PHE) is a derivative of the anticancer drug dolasta
tin 10 (dolavaline-valine-dolaisoleuine-dolaproine-dolaphenine). Broth micr
odilution assays with a wide variety of yeast and filamentous fungal specie
s demonstrated the specificity of auristatin PHE for Cryptococcus neoforman
s and several species of Trichosporon. The duration of the postantifungal e
ffect (PAFE) for C neoformans was determined for exposure times ranging fro
m 30 min to 2 h. For the derivative, a PAFE was detectable after 45 min of
exposure. The effect plateaued after I h of exposure, with a PAFE of approx
imately 6.5 h at four or eight times the auristatin PHE MIC. In contrast, t
here was no measurable PAFE after I h of exposure to dolastatin 10. Human s
erum greatly prolonged the PAFE of auristatin PHE at eight times the MIC. A
uristatin PHE arrested C. neoformans in the budding stage, possibly due to
a tubulin-inhibitory action. Auristatin PHE has potential as a narrow-spect
rum fungicidal agent and as a probe that can be used to study cryptococcal
cell division.