3 -ARILIDENE-2-OXYNDOLE DERIVATIVES AS MELATONIN ANALOGUES WITH ANTIOXIDANT AND INTRAOCULAR PRESSURE LOWERING PROPERTIES

Aim.Glaucoma is a whole group of diseases caused by increased intraocular pressure (IOP), leading to atrophy the optic nerve and irreversible blindness. Melatonin has wide range biological activity, including antioxidant antiglaucoma, but its use limited insufficient stability duration action. To search for new, more effective antiglaucoma agents among derivatives 3-arylidene-2-oxindole, melatonin analogues, quinonoxidoreductase 2 (NQO2) inhibitors was performed, activity determined effect active compounds on studied.Materials methods.The study inhibitory against NQO2 evaluated kinetically using menadione N-benzyl-dihydronicotinamide assubstrate co-substrate, respectively. Antiradical studied reducing superoxide-dependentluminescence in reaction medium containing hemoglobin, luminol hydrogen peroxide Infinite M200 PRO microplate reader (Tecan, Austria), as well free radical binding tests OH•-, ABTS DPPH. Cytotoxicity assessment carried out standard MTT test MCF-7 HepG2 line cells. Intraocular laboratory animals measured contactveterinary tonometer Tonovet (Finland).Results.Derivatives 3-arylidene-2-oxindole have demonstrated significant activity. A number also been identified. The most compound inhibits human with an IC50of 0,4 μM. showed anti-radical superoxide anion 6,1 μM, superior both counts, low cytotoxicity. With topical application 0,4% solution, reduced intact rats (40,9 ± 6,4) %, while not having systemic hypotensive effect.Conclusion.Derivatives are promising drug discovery treatment eye associatedwith or oxidative stress, such glaucoma, uveitis diabetic retinopathy.