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Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs

Tommaso Felicetti1, Violetta Cecchetti1, Giuseppe Manfroni1

  • 1Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, 06123 Perugia, Italy.

Journal of Medicinal Chemistry
|July 17, 2020
PubMed

Insights

Enoxacin enhances microRNA maturation, offering a novel therapeutic strategy for diseases linked to RNA interference pathway dysregulation. Its potential as a chemical template for drug development is explored.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Genetics

Background:

  • RNA interference (RNAi) is a fundamental biological process regulating gene expression via short non-coding RNAs.
  • Dysregulation of RNAi pathways, particularly microRNAs, is implicated in various human diseases.
  • Enoxacin is identified as the first small-molecule enhancer of microRNA (SMER) maturation.

Purpose of the Study:

  • To elucidate the biological activity and innovative mechanism of action of enoxacin as a SMER.
  • To assess the therapeutic potential of enoxacin in treating diseases associated with microRNA dysregulation.
  • To evaluate enoxacin as a chemical template for medicinal chemistry and drug discovery.

Main Methods:

  • Review and discussion of existing literature on enoxacin's biological activity.
  • Molecular-level analysis of enoxacin's mechanism of action as a SMER.
  • Exploration of structure-activity relationships and potential for chemical optimization.

Main Results:

  • Enoxacin demonstrates a unique mode of action in enhancing microRNA maturation.
  • The study highlights enoxacin's potential for therapeutic applications in various diseases.
  • Enoxacin serves as a valuable chemical scaffold for developing novel SMERs.

Conclusions:

  • Enoxacin represents a pioneering SMER with significant therapeutic promise.
  • Further research into enoxacin and related quinolones could lead to new drug development strategies.
  • The development of quinolone-based SMERs presents both opportunities and challenges for medicinal chemists.

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