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Abstract #106461 Published in IGR 23-3
Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and HS Donors
Sparaco R; Citi V; Magli E; Martelli A; Piragine E; Calderone V; Andreozzi G; Perissutti E; Frecentese F; Santagada V; Caliendo G; Severino B; Corvino A; Fiorino FInternational journal of molecular sciences 2022; 23:
Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (HS) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and HS donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different HS donors. The HS-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds , and were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of HS by antiglaucoma HS donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.
Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
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