Identification of Deferasirox as a Potential Carbonic Anhydrase II Inhibitor for Glaucoma treatment via Virtual Screening
Journal of Ophthalmic and Optometric Sciences,
Vol. 6 No. 1 (2022),
30 Khordad 2023
,
Page 28-41
https://doi.org/10.22037/joos.v6i1.42856
Abstract
Background: Systemic or topical administration of sulfonamide-containing carbonic anhydrase (CA) inhibitors is currently one of the lowering IOP approaches to treat glaucoma. Carbonic anhydrase II is an eye-expressed CA isoenzyme and has a major role in aqueous humor production.
Material and Methods: To identify new CA II inhibitors, the receptor-based virtual screening was performed using DrugRep server and its FDA-approved drug library. The crystal structure of human CA II (3HS4) was utilized as the receptor. The physicochemical, pharmacokinetic, and drug-likeness properties of 15 top-ranked inhibitors were then investigated by SwissADME server.
Results: The results showed that 200 recognized inhibitors interact with CA II active site with high binding affinities (-10.1 to -7.2 kcal/mol). 9 out of 15 top compounds (antrafenine, doxycycline, sitagliptin, benzhydrocodone, lumacaftor, deferasirox, lemborexant, talazoparib, selinexor, enasidenib, rolapitant, cyclothiazide, bendroflumethiazide, chlorthalidone, and quinupramine) possess fluorine atoms and 3 of them have the sulfonamide group in their structure. Based on the results, deferasirox is suggested as a promising candidate for further studies. This moderately soluble compound, which does not have fluorine atoms or a sulfonamide group in its structure, exhibits high bioavailability and GI absorption. Deferasirox is not a blood-brain barrier permeant and P-glycoprotein substrate and does not inhibit any CYP isoforms.
Conclusion: Deferasirox is suggested as a good candidate for glaucoma treatment. However, many further studies are required in this regard.
- Glaucoma
- Carbonic Anhydrase II (CA II) Inhibitors
- Virtual Screening
- DrugRep Server
- SwissADME Server
- 2023-11-08 (3)
- 2022-01-01 (2)
- 2023-11-08 (1)
How to Cite
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