2. Academic Validation
  3. Synthesis and biological evaluation of semi-synthetic albocycline analogs

Synthesis and biological evaluation of semi-synthetic albocycline analogs

  • Bioorg Med Chem Lett. 2020 Nov 1;30(21):127509. doi: 10.1016/j.bmcl.2020.127509.
Samer S Daher 1,  Kevin P Franklin 1,  Tyler Scherzi 2,  Paul M Dunman 2,  Rodrigo B Andrade 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Temple University, Philadelphia, PA 19122, United States.
  • 2 Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States.
  • 3 Department of Chemistry, Temple University, Philadelphia, PA 19122, United States. Electronic address: randrade@temple.edu.
PMID: 32827630 DOI: 10.1016/j.bmcl.2020.127509
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.

Keywords

Albocycline; Antibiotic; MIC; SAR.

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