Synthesis and biological evaluation of semi-synthetic albocycline analogs.

Abstract:

:Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a novel series analogs derived from albocycline by functionalization at three specific sites: the C2-C3 enone, the tertiary carbinol at C4, and the allylic C16 methyl group. Exploration of the structure-activity relationships (SAR) by means of minimum inhibitory concentration assays (MICs) revealed that C4 ester analog 6 was twice as potent as ALB, which represents a class of lead compound that can be further studied to address multi-drug resistant pathogens.

journal_name

Bioorg Med Chem Lett

authors

Daher SS,Franklin KP,Scherzi T,Dunman PM,Andrade RB

doi

10.1016/j.bmcl.2020.127509

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

127509

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30620-X

journal_volume

30

pub_type

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