{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:01:49Z","timestamp":1791925309882,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taif University Researchers Supporting","award":["TURSP-2020\/330"],"award-info":[{"award-number":["TURSP-2020\/330"]}]},{"name":"Taif University Researchers Supporting","award":["22UQU4331100DSR13"],"award-info":[{"award-number":["22UQU4331100DSR13"]}]},{"name":"Taif University, Taif, Saudi Arabia","award":["TURSP-2020\/330"],"award-info":[{"award-number":["TURSP-2020\/330"]}]},{"name":"Taif University, Taif, Saudi Arabia","award":["22UQU4331100DSR13"],"award-info":[{"award-number":["22UQU4331100DSR13"]}]},{"name":"Deanship of Scientific Research at Umm Al-Qura University","award":["TURSP-2020\/330"],"award-info":[{"award-number":["TURSP-2020\/330"]}]},{"name":"Deanship of Scientific Research at Umm Al-Qura University","award":["22UQU4331100DSR13"],"award-info":[{"award-number":["22UQU4331100DSR13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both the MMP-2 and MMP-9 proteins to find the most promising inhibitors as a proposed computational mechanism to treat keratoconus. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, and MMP inhibitors (MMPIs) are usually designed to interact with zinc ion in the catalytic (CAT) domain, thus interfering with enzymatic activity. In our research work, the FDA-approved ophthalmic medications will be investigated as MMPIs, to explore if they can be repurposed for KC treatment. The obtained findings of the docking study suggest that atenolol and ampicillin are able to accommodate into the active sites of MMP-2 and MMP-9. Additionally, both exhibited binding modes similar to inhibitors used as references, with an ability to bind to the zinc of the CAT. Molecular dynamic simulations and the MM-GBSA binding free-energy calculations revealed their stable binding over the course of 50 ns. An additional pharmacophoric study was carried out on MMP-9 (PDB ID: 1GKC) using the co-crystallized ligand as a reference for the future design and screening of the MMP-9 inhibitors. These promising results open the door to further biological research to confirm such theoretical results.<\/jats:p>","DOI":"10.3390\/molecules27113584","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"3584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1045-0163","authenticated-orcid":false,"given":"Amany","family":"Belal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1784-8572","authenticated-orcid":false,"given":"Mohamed A.","family":"Elanany","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Y.","family":"Santali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-6073","authenticated-orcid":false,"given":"Ahmed A.","family":"Al-Karmalawy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9489-3545","authenticated-orcid":false,"given":"Moustafa O.","family":"Aboelez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-602X","authenticated-orcid":false,"given":"Ali H.","family":"Amin","sequence":"additional","affiliation":[{"name":"Deanship of Scientific Research, Umm Al-Qura University, Makkah 21955, Saudi Arabia"},{"name":"Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-4749","authenticated-orcid":false,"given":"Magda H.","family":"Abdellattif","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-5380","authenticated-orcid":false,"given":"Ahmed B. M.","family":"Mehany","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-6703","authenticated-orcid":false,"given":"Hazem","family":"Elkady","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.clae.2010.04.006","article-title":"Keratoconus: A review","volume":"33","author":"Wolffsohn","year":"2010","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/eye.2013.278","article-title":"The pathogenesis of keratoconus","volume":"28","author":"Davidson","year":"2014","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-vision-121219-081723","article-title":"Genetic and Environmental Risk Factors for Keratoconus","volume":"6","author":"Lucas","year":"2020","journal-title":"Annu. 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