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The potential of chalcone derivatives as human carbonic anhydrase inhibitors in the therapy of glaucoma

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Abstract

Despite the significant development of diagnostic procedures and therapeutic options in past few decades, glaucoma is still highly prevalent and represents one of the leading causes of blindness in the world due to progressive and irreversible changes in optic nerve. Detection of carbonic anhydrase as a suitable target for the control of intraocular pressure indicated the beginning of carbonic anhydrase inhibitors application for the antiglaucoma treatment. Considering the multitude of proven and potential therapeutic applications of carbonic anhydrase inhibitors, the discovery of new chemotypes with carbonic anhydrase inhibitory activity will continue to be a significant aim. In this article we review the literature on synthetic chalcones as human carbonic anhydrase inhibitors, discussing their possible application focusing on chemical structure and Ki experimental values. From currently available experimental data and from the results we have obtained performing in silico calculations, we generated data collection on the basis of which we proposed 14 compounds of particular interest for further lead optimization and drug CAI development. Having previously experimentally determined excellent hCA II selectivity and strong inhibition effect and in our study predicted favorable physicochemical, pharmacokinetic, and toxicological profiles, a benzoxazolone chalcone derivative (139) stands out among the selected compounds. To examine potential therapeutic application, this candidate may be taken for further evaluation in in vivo studies.

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Funding

The work was funded by the Ministry of Science and Technological Development of Serbia (Project 451-03-68/2022-14/200113) and Faculty of Medicine, University of Niš Internal project No. 40.

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  1. Faculty of Medicine, University of Niš, Bulevar Dr Zorana Đinđića 81, 18000, Niš, Serbia

    Valentina Gocić

  2. Department of Pharmacy, Faculty of Medicine, University of Niš, Bulevar Dr Zorana Đinđića 81, 18000, Niš, Serbia

    Ana Marković

  3. Department of Chemistry, Faculty of Medicine, University of Niš, Bulevar Dr Zorana Đinđića 81, 18000, Niš, Serbia

    Jelena Lazarević

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Gocić, V., Marković, A. & Lazarević, J. The potential of chalcone derivatives as human carbonic anhydrase inhibitors in the therapy of glaucoma. Med Chem Res 31, 2103–2118 (2022). https://doi.org/10.1007/s00044-022-02978-9

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