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Highly potent, broadly active antifungal agents for the treatment of invasive fungal infections.

Abstract：

:Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins that have distinct advantages over peptides for pharmaceutical uses. Here we report the chemical optimization of bis-guanidine analogs focused on alterations of the central aryl core and the connection of it to the terminal guanidines. This effort resulted in the production of highly potent, broadly active compounds with low mammalian cell cytotoxicity that have comparable or improved antifungal activities over SOC agents. One optimal compound was also found to possess favourable in vitro pharmaceutical and off-target properties suitable for further development.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Baugh SDP,Chaly A,Weaver DG,Pelletier JC,Thanna S,Freeman KB,Reitz AB,Scott RW

doi

10.1016/j.bmcl.2020.127727

subject

Has Abstract

pub_date

2020-12-13 00:00:00

pages

127727

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30838-6

journal_volume

33

pub_type

杂志文章

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