Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, November 1998, p. 2961-2965, Vol. 42, No. 11
Cancer Research Institute and Departments of
Microbiology and Chemistry, Arizona State University, Tempe,
Arizona 85287-1604,1 and
Department of
Pathology, University of Virginia Medical Center, Charlottesville,
Virginia 229082
Received 9 April 1998/Returned for modification 6 May 1998/Accepted 1 September 1998
The biosynthetic peptide dolastatin 10 is currently in
phase I and II cancer clinical trials. We evaluated the antifungal spectrum of dolastatin 10 and four structural modifications. In broth macrodilution assays, the peptides were fungicidal for American Type Culture Collection strains and clinical isolates (including fluconazole-resistant strains) of Cryptococcus neoformans
but no other yeasts or filamentous fungi examined. Specificity for C. neoformans was also demonstrated in the solid-phase
disk diffusion assay, and fungicidal activity was confirmed in
time-kill experiments. For a methyl ester modification, the MICs at
which 50 and 90% of 19 clinical isolates were inhibited
(MIC50 and MIC90, respectively) were 0.195 and
0.39 µg/ml, respectively. The MFC50 (50% minimum fungicidal concentration) for this peptide was 0.39 µg/ml, and the
MFC90 was 0.78 µg/ml. MICs and MFCs were identical or
lower in the presence of human serum but increased with lowered pH. These peptides should be pursued as potential chemotherapeutics for
C. neoformans, a leading cause of infection and
mortality in immunocompromised patients.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Specific Activities of Dolastatin 10 and Peptide
Derivatives against Cryptococcus neoformans
*
Corresponding author. Mailing address: Cancer Research
Institute, Arizona State University, Tempe AZ 85287-1604. Phone: (602) 965-4907. Fax: (602) 965-8558. E-mail: pettitr{at}asu.edu.
Antimicrobial Agents and Chemotherapy, November 1998, p. 2961-2965, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Woyke, T., Berens, M. E., Hoelzinger, D. B., Pettit, G. R., Winkelmann, G., Pettit, R. K.
(2004). Differential Gene Expression in Auristatin PHE-Treated Cryptococcus neoformans. Antimicrob. Agents Chemother.
48: 561-567
[Abstract] [Full Text] -
Amador, M. L., Jimeno, J., Paz-Ares, L., Cortes-Funes, H., Hidalgo, M.
(2003). Progress in the development and acquisition of anticancer agents from marine sources. Ann Oncol
14: 1607-1615
[Full Text] -
Woyke, T., Roberson, R. W., Pettit, G. R., Winkelmann, G., Pettit, R. K.
(2002). Effect of Auristatin PHE on Microtubule Integrity and Nuclear Localization in Cryptococcus neoformans. Antimicrob. Agents Chemother.
46: 3802-3808
[Abstract] [Full Text] -
Woyke, T., Pettit, G. R., Winkelmann, G., Pettit, R. K.
(2001). In Vitro Activities and Postantifungal Effects of the Potent Dolastatin 10 Derivative Auristatin PHE. Antimicrob. Agents Chemother.
45: 3580-3584
[Abstract] [Full Text] -
Vaishampayan, U., Glode, M., Du, W., Kraft, A., Hudes, G., Wright, J., Hussain, M.
(2000). Phase II Study of Dolastatin-10 in Patients with Hormone-refractory Metastatic Prostate Adenocarcinoma. Clin. Cancer Res.
6: 4205-4208
[Abstract] [Full Text] -
Andriole, V. T.
(1999). Current and future antifungal therapy: new targets for antifungal agents. J Antimicrob Chemother
44: 151-162
[Abstract] [Full Text]
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»