title: Bactericidal kinetics of marine-derived napyradiomycins against contemporary methicillin-resistant Staphylococcus aureus.
abstract: There is an urgent need for new antibiotics to treat hospital- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous work has indicated that both terrestrial and marine-derived members of the napyradiomycin class possess potential anti-staphylococcal activities. These compounds are unique meroterpenoids with unusual levels of halogenation. In this paper we report the evaluation of two previously described napyradiomycin derivatives, A80915A (1) and A80915B (2) produced by the marine-derived actinomycete, Streptomyces sp. strain CNQ-525, for their specific activities against contemporary and clinically relevant MRSA. Reported are studies of the in vitro kinetics of these chemical scaffolds in time-kill MRSA assays. Both napyradiomycin derivatives demonstrate potent and rapid bactericidal activity against contemporary MRSA strains. These data may help guide future development and design of analogs of the napyradiomycins that could potentially serve as useful anti-MRSA therapeutics.
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.|Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Nina M
authors: NM
authors: Haste
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.|Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Lauge
authors: L
authors: Farnaes
authors: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Varahenage R
authors: VR
authors: Perera
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.|Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
authors: William
authors: W
authors: Fenical
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.|Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Victor
authors: 0000-0003-3847-0422
authors: V
authors: Nizet
authors: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Mary E
authors: ME
authors: Hensler
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D009285:Naphthoquinones / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism*
chemical_list: C562098:A80915B; D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; C071895:A 80915A