Design and Synthesis of Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors.

ABSTRACT: The molecular chaperone Hsp90, essential in all eukaryotes, plays a multifaceted role in promoting survival, virulence, and drug resistance across diverse pathogenic fungal species. The chaperone is also critically important, however, to the pathogen's human host, preventing the use of known clinical Hsp90 inhibitors in antifungal applications due to concomitant host toxicity issues. With the goal of developing Hsp90 inhibitors with acceptable therapeutic indices for the treatment of invasive fungal infections, we initiated a program to design and synthesize potent inhibitors with selective activity against fungal Hsp90 isoforms over their human counterparts. Building on our previously reported derivatization of resorcylate natural products to produce fungal-selective compounds, we have de

SUBMITTER: Huang DS 

PROVIDER: S-EPMC7069776 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature