title: Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (III).
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.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Drug Discovery, College of Pharmacy, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA. Jerry.Li@ucsf.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA. nhaste@ucsd.edu.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Haste
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA. wdee.ucsd@gmail.com.
authors.forename: Wdee
authors.initials: W
authors.lastname: Thienphrapa
authors.affiliation: Department of Drug Discovery, Chemical Biology & Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Jerry.Li@ucsf.edu.
authors.forename: Jerry
authors.initials: J
authors.lastname: Li
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA. vnizet@ucsd.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA. mhensler@ucsd.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Hensler
authors.affiliation: Department of Pharmaceutical Sciences, Center for Drug Discovery, College of Pharmacy, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA. Rongshi.Li@unmc.edu.
authors.forename: Rongshi
authors.initials: R
authors.lastname: Li
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011758:Pyrroles; C528298:marinopyrrole A