Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy

Suchismita Acharya; Preston Rogers; Raghu R. Krishnamoorthy; Dorota L. Stankowska; H. V.Rasika Dias; Thomas Yorio

doi:10.1016/j.bmcl.2015.12.030

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy

Suchismita Acharya, Preston Rogers, Raghu R. Krishnamoorthy, Dorota L. Stankowska, H. V.Rasika Dias, Thomas Yorio

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Pages (from-to)	1490-1494
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2015.12.030
State	Published - 1 Mar 2016

Keywords

Aceloxy acyl carbamate prodrug
Catalytic anti-oxidant
Glaucoma
Nitric oxide
Optic neuropathy
SOD mimetic
Sydnonimine
TEMPOL

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10.1016/j.bmcl.2015.12.030

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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.",

keywords = "Aceloxy acyl carbamate prodrug, Catalytic anti-oxidant, Glaucoma, Nitric oxide, Optic neuropathy, SOD mimetic, Sydnonimine, TEMPOL",

author = "Suchismita Acharya and Preston Rogers and Krishnamoorthy, {Raghu R.} and Stankowska, {Dorota L.} and Dias, {H. V.Rasika} and Thomas Yorio",

note = "Funding Information: We thank The University of Texas at Arlington and Welch Foundation ( Y-1289 ) – United States for support of this research. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd. All rights reserved.",

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doi = "10.1016/j.bmcl.2015.12.030",

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AU - Acharya, Suchismita

AU - Rogers, Preston

AU - Krishnamoorthy, Raghu R.

AU - Stankowska, Dorota L.

AU - Dias, H. V.Rasika

AU - Yorio, Thomas

N1 - Funding Information: We thank The University of Texas at Arlington and Welch Foundation ( Y-1289 ) – United States for support of this research. Publisher Copyright: © 2016 Elsevier Ltd. All rights reserved.

PY - 2016/3/1

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N2 - 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.

AB - 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.

KW - Aceloxy acyl carbamate prodrug

KW - Catalytic anti-oxidant

KW - Glaucoma

KW - Nitric oxide

KW - Optic neuropathy

KW - SOD mimetic

KW - Sydnonimine

KW - TEMPOL

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SN - 0960-894X

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EP - 1494

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy

Abstract

Keywords

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