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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.

SUBMITTER: Daher SS

PROVIDER: S-EPMC7577960 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Synthesis and biological evaluation of semi-synthetic albocycline analogs.

Daher Samer S SS Franklin Kevin P KP Scherzi Tyler T Dunman Paul M PM Andrade Rodrigo B RB

Bioorganic & medicinal chemistry letters 20200819 21

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 ...[more]

PMID: 32827630

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