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Semisynthetic Natural Products for Antibacterial Drug Discovery
Author(s) -
Lee Richard
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.392.2
Subject(s) - natural product , drug discovery , antibiotics , drug , efflux , computational biology , microbiology and biotechnology , biology , pharmacology , biochemical engineering , bioinformatics , engineering , genetics , biochemistry
The pressing need for new treatments for multi‐drug resistant bacterial infections including MDR and XDR tuberculosis has led us to re‐explore the use of natural product antibiotics not normally used to treat target infections, especially those with unique mechanisms of action. Being the product of combinatorial evolution natural products have many advantages over purely synthetic antibacterial leads, but also some notable disadvantages often in regard to spectrum and human metabolism. This presentation will go over our efforts to advance under‐explored antibiotic scaffolds with semi‐synthetic approaches to tackle these disadvantages. Using spectinomycin as an example, synthetic modifications have been applied to overcome native bacterial efflux leading to potent leads with better than predicted in vivo efficacy in complex infection models. These observations have led us to examine active uptake and slow‐growing pathogen targeting hypotheses that are hard wired into many natural products, which are very hard to replicate by direct purely synthetic de novo antibacterial drug design. Support or Funding Information This work was supported by research grant R01AI090810 by the National Institutes of Health and the American Lebanese Syrian Associated Charities (ALSAC)