Synthesis of new heterocyclic derivatives (benzodioxane-2-yl)methanol and their effect on rat intraocular pressure

Abstract

Objective: Synthesis of new compounds, melatonin isosters, and study of their ability to reduce intraocular pressure. Materials and methods: Based on the previously made forecast and on the similarity with the selected compounds, the synthesis of new compounds was carried out – melatonin isosters having a 2,3-dihydro-1,4-benzodioxin cycle connected by a linker of various chemical structure with a nitrogen-containing heterocyclic core. The structure of the synthesized compounds was proved by 1H- and 13C- NMR spectroscopy, purity and individuality – by chromatographic methods. Intraocular pressure in laboratory animals was measured using a contact veterinary tonometer Tonovet (Finland). Cytotoxicity was assessed using MTT test on normal rat skin fibroblasts. Results: Derivatives (benzodioxane-2-yl)methanol reduced the level of IOP in varying degrees of severity. The VMA-22-37 compound showed the greatest activity. With topical application of a 0.4% solution, the compound reduced the intraocular pressure of intact rats by 26.6%, while not affecting the control eye. This compound also has low cytotoxicity. Conclusion: Derivatives (benzodioxane-2-yl)methanol is promising for the search for compounds capable of reducing increased intraocular pressure.