Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±)-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR) studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33) of marinopyrrole A is ≥63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.
Original language | English (US) |
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Pages (from-to) | 2927-2948 |
Number of pages | 22 |
Journal | Marine Drugs |
Volume | 11 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2013 |
Keywords
- Antibiotics
- MRSA
- MRSE
- MSSA
- Marinopyrroles
- SAR
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)