title: Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.
abstract: Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Acharya
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Preston
authors.initials: P
authors.lastname: Rogers
authors.affiliation: North Texas Eye Research Institute (NTERI), University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Raghu R
authors.initials: RR
authors.lastname: Krishnamoorthy
authors.affiliation: North Texas Eye Research Institute (NTERI), University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Dorota L
authors.initials: DL
authors.lastname: Stankowska
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: H V Rasika
authors.initials: HV
authors.lastname: Dias
authors.affiliation: Department of Pharmacology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yorio
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013558:Sydnones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011355:Prodrugs; D017382:Reactive Oxygen Species; D013558:Sydnones; D009569:Nitric Oxide; D006861:Hydrogen Peroxide
keywords: Aceloxy acyl carbamate prodrug; Catalytic anti-oxidant; Glaucoma; Nitric oxide; Optic neuropathy; SOD mimetic; Sydnonimine; TEMPOL