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Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase

Nicholas Simon1, Matthew L Bochman, Sandlin Seguin1

  • 1*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.

Bioscience Reports
|September 5, 2013
PubMed

Insights

The antibiotic ciprofloxacin specifically inhibits the Mcm2-7 helicase, a key DNA replication protein. This finding supports developing targeted Mcm2-7 inhibitors for cancer therapy and research.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Current DNA replication inhibitors lack specificity, causing side effects and limiting research utility.
  • Targeting specific components like Mcm2-7 is crucial for developing precise inhibitors.

Purpose of the Study:

  • To identify specific inhibitors of the Mcm2-7 helicase, a core component of DNA replication.
  • To explore the potential of ciprofloxacin and related compounds as Mcm2-7 inhibitors.

Main Methods:

  • Enzyme assays to test ciprofloxacin's effect on Mcm2-7 helicase activity.
  • Cell proliferation assays in yeast and human cells.
  • Screening of ciprofloxacin analogs for enhanced Mcm2-7 inhibition.

Main Results:

  • Ciprofloxacin selectively inhibits Mcm2-7 helicase activity in vitro.
  • Inhibition of Mcm2-7 by ciprofloxacin correlates with reduced cell proliferation.
  • A specific mcm mutant displayed resistance to ciprofloxacin, confirming target engagement.

Conclusions:

  • Ciprofloxacin is a specific inhibitor of the Mcm2-7 helicase.
  • Quinolone-based compounds show promise for developing targeted Mcm2-7 inhibitors for therapeutic and research applications.

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