1. Isolation of the antibiotic pseudopyronine B and SAR evaluation of C3/C6 alkyl analogs.
- Author
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Bouthillette LM, Darcey CA, Handy TE, Seaton SC, and Wolfe AL
- Subjects
- Anti-Bacterial Agents chemistry, Anti-Bacterial Agents isolation & purification, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Molecular Structure, Pseudomonas chemistry, Pyrones chemistry, Pyrones isolation & purification, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Pyrones pharmacology
- Abstract
Natural products are an abundant source of structurally diverse compounds with antibacterial activity that can be used to develop new and potent antibiotics. One such class of natural products is the pseudopyronines. Here we present the isolation of pseudopyronine B (2) from a Pseudomonas species found in garden soil in Western North Carolina, and SAR evaluation of C3 and C6 alkyl analogs of the natural product for antibacterial activity against Gram-positive and Gram-negative bacteria. We found a direct relationship between antibacterial activity and C3/C6 alkyl chain length. For inhibition of Gram-positive bacteria, alkyl chain lengths between 6 and 7 carbons were found to be the most active (IC
50 =0.04-3.8µg/mL) whereas short alkyl chain analogs showed modest activity against Gram-negative bacteria (IC50 =223-304µg/mL). This demonstrates the potential for this class of natural products to be optimized for selective activity against either Gram-positive or Gram-negative bacteria., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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