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Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors
Kundansingh A Pardeshi1, Satish R Malwal1, Ankita Banerjee2
1Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune 411 008, Maharashtra, India.
Abstract:
Drug resistant infections are becoming common worldwide and new strategies for drug development are necessary. Here, we report the synthesis and evaluation of 2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a reactive sulfur species, as methicillin-resistant Staphylococcus aureus (MRSA) inhibitors. N-(3-Methoxyphenyl)-2,4-dinitro-N-(prop-2-yn-1-yl)benzenesulfonamide (5e) was found to have excellent in vitro MRSA inhibitory potency. This compound is cell permeable and treatment of MRSA cells with 5e depleted intracellular thiols and enhanced oxidative species both results consistent with a mechanism involving thiol activation to produce SO2.
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