1. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (III)
- Author
-
Yan Liu, Nina Haste, Wdee Thienphrapa, Jerry Li, Victor Nizet, Mary Hensler, and Rongshi Li
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Medicinal & Biomolecular Chemistry ,Molecular Conformation ,Pharmaceutical Science ,MRSA ,Microbial Sensitivity Tests ,In Vitro Techniques ,01 natural sciences ,Article ,antibiotics ,Vaccine Related ,non-symmetrical marinopyrroles ,SAR ,03 medical and health sciences ,Structure-Activity Relationship ,Biodefense ,Drug Discovery ,Humans ,Pyrroles ,lcsh:QH301-705.5 ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,0303 health sciences ,010405 organic chemistry ,030306 microbiology ,Prevention ,Pharmacology and Pharmaceutical Sciences ,0104 chemical sciences ,3. Good health ,Anti-Bacterial Agents ,Emerging Infectious Diseases ,Infectious Diseases ,lcsh:Biology (General) ,5.1 Pharmaceuticals ,Antimicrobial Resistance ,Development of treatments and therapeutic interventions ,Infection ,Physical Chemistry (incl. Structural) - Abstract
The marine natural product, marinopyrrole A (1), was previously shown to have significant antibiotic activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Although compound (1) exhibits a significant reduction in MRSA activity in the presence of human serum, we have identified key modifications that partially restore activity. We previously reported our discovery of a chloro-derivative of marinopyrrole A (1a) featuring a 2–4 fold improved minimum inhibitory concentration (MIC) against MRSA, significantly less susceptibility to serum inhibition and rapid and concentration-dependent killing of MRSA. Here, we report a novel fluoro-derivative of marinopyrrole A (1e) showing an improved profile of potency, less susceptibility to serum inhibition, as well as rapid and concentration-dependent killing of MRSA.
- Published
- 2014