Discovery of bicyclic inhibitors against menaquinone biosynthesis

Seoung Ryoung Choi, Marilynn A Larson, Steven Heye Hinrichs, Amanda M. Bartling, Joel Frandsen, Prabagaran Narayanasamy

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Introduction: Menaquinone is used for transporting electrons and is essential for the aerobic and anaerobic respiratory systems of all pathogens and prokaryotes. Many Gram-positive bacteria use only menaquinone in the electron transport system. Thus, menaquinone biosynthesis is a potential target for the development of inhibitors against bacteria including drug-resistant pathogens. Results: After modeling, synthesis and in vitro testing, we determined that 7-methoxy-2-naphthol-based inhibitors targeted the MenA enzyme of the menaquinone biosynthesis pathway. The developmental compounds 1 and 2 were active against Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration of 3-5 μg/ml. Conclusion: Nontraditional bicyclic inhibitors, compounds 1 and 2 could serve as lead compounds for the development of an antimicrobial agent, with activities against M. tuberculosis and methicillin-resistant S. aureus.

Original languageEnglish (US)
Pages (from-to)11-16
Number of pages6
JournalFuture Medicinal Chemistry
Volume8
Issue number1
DOIs
StatePublished - Jan 2016

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Vitamin K 2
Methicillin-Resistant Staphylococcus aureus
Mycobacterium tuberculosis
Gram-Positive Bacteria
Electron Transport
Anti-Infective Agents
Respiratory System
Electrons
Bacteria
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Discovery of bicyclic inhibitors against menaquinone biosynthesis. / Choi, Seoung Ryoung; Larson, Marilynn A; Hinrichs, Steven Heye; Bartling, Amanda M.; Frandsen, Joel; Narayanasamy, Prabagaran.

In: Future Medicinal Chemistry, Vol. 8, No. 1, 01.2016, p. 11-16.

Research output: Contribution to journalArticle

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