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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. Modes of action of the new arylguanidine abafungin beyond interference with ergosterol biosynthesis and in vitro activity against medically important fungi
Background: In contrast to the increasing numbers of agents for the
treatment of invasive fungal infections, discoveries of new
antifungal agents with therapeutic value in dermatomycoses are
reported only rarely. Methods: Abafungin (chemical abstracts
service registry No. 129639-79/8) is the first member of a novel
class of synthetic antifungal compounds, the arylguanidines. It was
first synthesized at Bayer AG, Leverkusen, Germany, and its
antifungal action was discovered during the screening of
H-2-receptor antagonists based on the structure of famotidine. To
obtain insight into its mode of action and antifungal activity,
various tests were carried out with different fungal pathogens in
vitro. Results: Abafungin was found to have potent antifungal
activity. Furthermore, mode-of-action studies suggested that
abafungin exerts its antifungal activity regardless of whether the
pathogens are growing or in a resting state. One target of
abafungin was found to be the inhibition of transmethylation at the
C-24 position of the sterol side chain, catalyzed by the enzyme
sterol-C-24-methyltransferase. A second action of abafungin seems
to be a direct effect on the fungal cell membrane. Conclusion: The
observed characteristics of abafungin indicate that abafungin might
be a promising antifungal agent defining a new class of
antimycotics. Copyright (C) 2008 S. Karger AG, Basel.

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„Modes of action of the new arylguanidine abafungin beyond interference with ergosterol biosynthesis and in vitro activity against medically important fungi“

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