{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:52:07Z","timestamp":1791021127033,"version":"4.1.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["PNURSP2022R26"],"award-info":[{"award-number":["PNURSP2022R26"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The aberrant expression of aldo keto reductases (AKR1B1 &amp; AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds <jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1\/AKR1B10 for curing colon cancer and related malignancies.<\/jats:p>","DOI":"10.1371\/journal.pone.0271602","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T17:56:36Z","timestamp":1666893396000},"page":"e0271602","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-7234","authenticated-orcid":true,"given":"Syeda Abida","family":"Ejaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pervez Rashid","family":"Birmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadijah Mohammedsalaeh","family":"Katubi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab Mufarreh","family":"Elqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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The Alkaloids","volume":"82","author":"PJ Boraty\u0144ski","year":"2019","journal-title":"Chemistry and Biology"},{"issue":"4","key":"pone.0271602.ref012","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1021\/cb200528z","article-title":"Iron (III) protoporphyrin IX complexes of the antimalarial cinchona alkaloids quinine and quinidine","volume":"7","author":"KA de Villiers","year":"2012","journal-title":"ACS Chemical Biology"},{"key":"pone.0271602.ref013","article-title":"Introductory chapter: alkaloids-their importance in nature and for human life. 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[Cambridge, Mass., U.S.A.]."},{"key":"pone.0271602.ref022","article-title":"Announcing the worldwide protein data bank","author":"H. Berman","year":"2003","journal-title":"Nature structural biology"},{"key":"pone.0271602.ref023","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity","volume":"30","author":"GM Morris","year":"2009","journal-title":"Journal of computational chemistry"},{"key":"pone.0271602.ref024","unstructured":"Molecular Operating Environment (MOE), 2015.10; Chemical Computing Group ULC: 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2016."},{"issue":"1","key":"pone.0271602.ref025","article-title":"Illustrated step by step protocol to perform molecular docking: Human estrogen receptor complex with 4-hydroxytamoxifen as a case study","volume":"3","author":"SU Khan","year":"2020","journal-title":"Progress in Drug Discovery & Biomedical Science"},{"issue":"32","key":"pone.0271602.ref026","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1002\/jcc.23094","article-title":"Fast force field\u2010based optimization of protein\u2013ligand complexes with graphics processor","volume":"33","author":"L Heinzerling","year":"2012","journal-title":"Journal of Computational Chemistry"},{"key":"pone.0271602.ref027","unstructured":"Visualizer, D.S., 2005. Accelrys software inc Discovery Studio Visualizer, 2."},{"key":"pone.0271602.ref028","article-title":"Molecular docking: current advances and challenges.","volume":"21","author":"FD Prieto-Mart\u00ednez","year":"2018","journal-title":"TIP. 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