Redesign of Fluoroquinolones to Catalytically Fragment Chromosomal DNA

Researcher:

Categories:

Chemistry and Materials | Pharmaceuticals and Biotechnology

The Technology

Fluoroquinolones are highly potent, broad spectrum antibiotics that are among the most prescribed antibacterial in the world. They exert a bacteriostatic effect by selectively binding to the bacterial topoisomerase IIA− DNA complex and thereby inhibiting DNA replication. At higher doses (5−10 × minimum inhibitory concentration (MIC)), they exert a bactericidal effect by causing fragmentation of the bacterial chromosome, which is toxic for the bacteria. However, the emergence of resistance is becoming a critical issue that is limiting the use of this class of antibiotics. Consequently, several novel bacterial topoisomerase type IIA inhibitors have been developed that retain potency against quinolone-resistance bacterial strains by offering an alternative binding mode or mechanism of action, including among others NXL101 and REDX07638. The invention is a catalytic antibiotic that is designed to cleave a specific, “critical” chemical bond in a bacterial target that is projected to result in the immediate deactivation of the target. Specifically, new derivatives of ciprofloxacin to act on its target in a catalytic manner.

Advantages

  • Improved potency
  • Lower toxicity
  • Delay of new resistance development by bacteria

Applications

  • New antibiotics
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Dr. Gal Gur
Director of Business Development, Life Sciences