Pradimicins: A novel class of broad-spectrum antifungal compounds

T. J. Walsh, N. Giri

Research output: Contribution to journalArticle

Abstract

Pradimicins are a new class of antifungal compounds currently undergoing preclinical and early phase I clinical trials. The pradimicin structure is characterized by an aglycone of dihydrobenzo (alpha) naphthacenequinone with substitutions by a D-amino acid and hexose sugar. Pradimicins possess a novel mechanism of action consisting of a specific binding recognition to terminal D-mannosides of the cell wall of Candida albicans, resulting in the formation of a ternary complex consisting of D-mannoside, pradimicin, and calcium that leads to disruption of the integrity of the fungal cell membrane. Pradimicin in the form of BMS-181184 has broad-spectrum in vitro antifungal activity against Candida spp., Cryptococcus neoformans, Aspergillus spp., dematiaceous molds, and the Zygomycetes. Fusarium spp. are comparatively resistant to high concentrations of pradimicin. Initial in vivo studies indicate that pradimicins have antifungal activity against experimental murine disseminated candidiasis and disseminated aspergillosis. Early studies indicate an excellent therapeutic index with no major end-organ toxicity. Pradimicins warrant further investigation for treatment of opportunistic mycoses in immunocompromised hosts.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalEuropean Journal of Clinical Microbiology and Infectious Diseases
Volume16
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Mannosides
Clinical Trials, Phase I
Cryptococcus neoformans
Hexoses
Aspergillosis
Mycoses
Candidiasis
Fusarium
Immunocompromised Host
Aspergillus
Candida albicans
Candida
Cell Wall
Fungi
Cell Membrane
Calcium
Amino Acids
pradimicin A
Therapeutics
pradimicin D

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology

Cite this

Pradimicins : A novel class of broad-spectrum antifungal compounds. / Walsh, T. J.; Giri, N.

In: European Journal of Clinical Microbiology and Infectious Diseases, Vol. 16, No. 1, 1997, p. 93-97.

Research output: Contribution to journalArticle

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