Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma

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dc.creatorAmankwa, Charles E.
dc.creatorGondi, Sudershan R.
dc.creatorDibas, Adnan Dibas
dc.creatorWeston, Courtney
dc.creatorFunk, Arlene
dc.creatorNguyen, Tam
dc.creatorNguyen, Kytai T.
dc.creatorEllis, Dorette Z.
dc.creatorAcharya, Suchismita
dc.creator.orcid0000-0002-1120-7053 (Amankwa, Charles E.)
dc.date.accessioned2022-08-18T18:32:06Z
dc.date.available2022-08-18T18:32:06Z
dc.date.issued2021-04-08
dc.description.abstractOxidative stress induced death and dysregulation of trabecular meshwork (TM) cells contribute to the increased intraocular pressure (IOP) in primary open angle (POAG) glaucoma patients. POAG is one of the major causes of irreversible vision loss worldwide. Nitric oxide (NO), a small gas molecule, has demonstrated IOP lowering activity in glaucoma by increasing aqueous humor outflow and relaxing TM. Glaucomatous pathology is associated with decreased antioxidant enzyme levels in ocular tissues causing increased reactive oxygen species (ROS) production that reduce the bioavailability of NO. Here, we designed, synthesized, and conducted in vitro studies of novel second-generation sulfur containing hybrid NO donor-antioxidants SA-9 and its active metabolite SA-10 to scavenge broad-spectrum ROS as well as provide efficient protection from t-butyl hydrogen peroxide (TBHP) induced oxidative stress while maintaining NO bioavailability in TM cells. To allow a better drug delivery, a slow release nanosuspension SA-9 nanoparticles (SA-9 NPs) was prepared, characterized, and tested in dexamethasone induced ocular hypertensive (OHT) mice model for IOP lowering activity. A single topical eye drop of SA-9 NPs significantly lowered IOP (61%) at 3 h post-dose, with the effect lasting up to 72 h. This class of molecule has high potential to be useful for treatment of glaucoma.
dc.description.sponsorshipThis work was supported by the Applied Research Seed grant (2400018) from UNTHSC, Bright Focus Foundation grant (G2018056) and from National Institute of Health (R01EY029823) awarded to SA.
dc.identifier.citationAmankwa, C. E., Gondi, S. R., Dibas, A., Weston, C., Funk, A., Nguyen, T., Nguyen, K. T., Ellis, D. Z., & Acharya, S. (2021). Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma. Antioxidants (Basel, Switzerland), 10(4), 575. https://doi.org/10.3390/antiox10040575
dc.identifier.issn2076-3921
dc.identifier.issue4
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31591
dc.identifier.volume10
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/antiox10040575
dc.rights.holder© 2021 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceAntioxidants (Basel)
dc.subjectglaucoma
dc.subjecthybrid small molecule
dc.subjectintra-ocular pressure
dc.subjectnanosuspension
dc.subjectnitric oxide
dc.subjectsuperoxide radical
dc.titleNovel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma
dc.typeArticle
dc.type.materialtext

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