Kibdelomycin A,a congener of kibdelomycin,derivatives and their antibacterial activities |
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Authors: | Sheo B Singh Michael A Goetz Scott K Smith Deborah L Zink Jon Polishook Russell Onishi Scott Salowe Judyann Wiltsie John Allocco Janet Sigmund Karen Dorso Mercedes de la Cruz Jesús Martín Francisca Vicente Olga Genilloud Robert GK Donald John W Phillips |
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Institution: | 1. Infectious Diseases, Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, USA;2. Medicinal Chemistry, Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, USA;3. Centro de Investigación Básica (CIBE), Merck Sharp & Dohme de España, S. A., Madrid, Spain |
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Abstract: | 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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