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Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

ABSTRACT: A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus) strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant S. aureus (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb S. aureus cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria.

SUBMITTER: Karanja CW

PROVIDER: S-EPMC9416421 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

Karanja Caroline W CW Naganna Nimishetti N Abutaleb Nader S NS Dayal Neetu N Onyedibe Kenneth I KI Aryal Uma U Seleem Mohamed N MN Sintim Herman O HO

Molecules (Basel, Switzerland) 20220810 16

A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant <i>Staphylococcus aureus (S. aureus)</i> strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant <i>S. aureus</i> (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear i ...[more]

PMID: 36014324

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Dataset Information

Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

Publications

Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

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