Kibdelomycin A, a congener of kibdelomycin, derivatives and their antibacterial activities
2012
Singh, Sheo B. | Goetz, Michael A. | Smith, Scott K. | Zink, Deborah L. | Polishook, Jon | Onishi, Russell | Salowe, Scott | Wiltsie, Judyann | Allocco, John | Sigmund, Janet | Dorso, Karen | de la Cruz, Mercedes | Martín, Jesús | Vicente, Francisca | Genilloud, Olga | Donald, Robert G.K. | Phillips, John W.
Emergence of bacterial resistance has eroded the effectiveness of many life saving antibiotics leading to an urgent need for new chemical classes of antibacterial agents. We have applied a Staphylococcus aureus fitness test strategy to natural products screening to meet this challenge. In this paper we report the discovery of kibdelomycin A, a demethylated congener of kibdelomycin, the representative of a novel class of antibiotics produced by a new strain of Kibdelosporangium. Kibdelomycin A is a potent inhibitor of DNA gyrase and topoisomerase IV, inhibits DNA synthesis and shows whole cell antibiotic activity, albeit, less potently than kibdelomycin. Kibdelomycin C-33 acetate and tetrahydro-bisdechloro derivatives of kibdelomycin were prepared which helped define a basic SAR of the family.
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