Oxindole-based intraocular pressure reducing agents. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Zaryanova, Ekaterina V.; Lozinskaya, Nataly A.; Beznos, Olga V.; Volkova, Maria S.; Chesnokova, Nataly B.; Zefirov, Nikolay S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 16(2017)
• Page Start: 3787
• Page End: 3793
• Publication Date: 2017-08-15
• Subjects: Melatonin -- Intraocular pressure -- Oxindole derivatives -- Glaucoma treatment; IOP intraocular pressure -- QR2 NQO2, quinone reductase 2 -- MCA-NAT 5-MCA-NAT - 5-methoxycarbonylamino-N-acetyltryptamine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.065
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The study represents the new findings at the crossroads of chemistry and medicine, particularly between medicinal and organic chemistry and ophthalmology. In this work we describe how the chemical reactivity of indolinone scaffold may be used to create small molecule ligands with strong biological response comparable with and larger than that of endogenous hormone. The synthesis of oxindole-based melatonin and 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) analogues was proposed and their ability to influence intraocular pressure (IOP) was studied in vivo . Time-dependent study revealed the prolonged effect (more than 6 h) of the lead-compound. This effect in combination with high IOP reducing effect (41 ± 6%) in low concentrations of the active compound (0.1 wt%) and with high water solubility represents a great potential of low-cost oxindole derivatives as potent antiglaucoma agents.