Panning commercial compound libraries for antifungals: can a University research lab succeed in finding novel leads?

Ref ID: 19429

Author:

N. Osherov,1 G. Mircus,2 D. Ben-Yaakov,2 A. Rivkin2 and Y.
Shadkchan2

Author address:

1Tel Aviv University, Israel and 2Clinical Microbiology and
Immunology, Israel

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

The number of life-threatening, invasive fungal infections has risen
dramatically over the last 20 years. Today, 4% of all patients dying in
modern tertiary care hospitals have invasive aspergillosis, while 2%
have invasive candidiasis. Existing treatments for invasive fungal infec-
tions remain unsatisfactory with an unacceptably high mortality rate
in high-risk patients. Therefore, there is an urgent and unmet need to
develop additional and novel antifungal drugs that inhibit essential
fungal-specific cellular targets and pathways. We have screened a
diverse commercial library of ~80,000 compounds to identify those
interfering with virulence-essential pathways including cell wall stabil-
ity, iron and zinc uptake, and synthesis of essential aromatic amino
acids, metabolic precursors and vitamins. Our results suggest that it is
possible to identify ’hit’ compounds specifically affecting most of these
pathways and inhibiting fungal growth at micromolar concentrations.
However, most are active only under defined conditions in vitro. The
implications of our findings will be discussed.

Abstract Number: p251

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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