Novel antifungal compounds discovered in Medicines for Malaria Venture's Malaria Box

Eric H. Jung, David J Meyers, Jürgen Bosch, Arturo Casadevalla

Research output: Contribution to journalArticle

Abstract

Similarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3Hbenzimidazol- 5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole against Cryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such as Lomentospora prolificans and Cryptococcus gattii. Antifungal activity was also observed against a common fungus, Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics.

Original languageEnglish (US)
Article numbere00537-17
JournalmSphere
Volume3
Issue number2
DOIs
StatePublished - Mar 1 2018

Fingerprint

Malaria
Pharmaceutical Preparations
Cryptococcus gattii
Drug Repositioning
Echinocandins
Polyenes
Azoles
Cryptococcus neoformans
Mycoses
Fluconazole
Candida albicans
Switzerland
Names
Immunity
Fungi
Infection
Therapeutics

Keywords

  • Antifungal agents
  • Candida albicans
  • Cryptococcus neoformans

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Novel antifungal compounds discovered in Medicines for Malaria Venture's Malaria Box. / Jung, Eric H.; Meyers, David J; Bosch, Jürgen; Casadevalla, Arturo.

In: mSphere, Vol. 3, No. 2, e00537-17, 01.03.2018.

Research output: Contribution to journalArticle

Jung, Eric H. ; Meyers, David J ; Bosch, Jürgen ; Casadevalla, Arturo. / Novel antifungal compounds discovered in Medicines for Malaria Venture's Malaria Box. In: mSphere. 2018 ; Vol. 3, No. 2.
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