title: Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors.
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.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune 411 008, Maharashtra, India.
authors.forename: Kundansingh A
authors.initials: KA
authors.lastname: Pardeshi
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune 411 008, Maharashtra, India.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Malwal
authors.affiliation: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad, C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad, C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Surobhi
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad, C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Radha
authors.initials: R
authors.lastname: Rangarajan
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pune 411 008, Maharashtra, India. Electronic address: harinath@iiserpune.ac.in.
authors.forename: Harinath
authors.initials: H
authors.lastname: Chakrapani
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D013458:Sulfur Dioxide / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D013458:Sulfur Dioxide
keywords: Drug resistance; MRSA; Reactive oxygen species; Sulfur dioxide; Thiol