{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:25Z","timestamp":1791244285689,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Oman Research Council (TRC)","award":["BFP\/RGP\/HSS\/18\/018"],"award-info":[{"award-number":["BFP\/RGP\/HSS\/18\/018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>\u03b1-Glucosidase is considered a prime drug target for Diabetes Mellitus and its inhibitors are used to delay carbohydrate digestion for the treatment of diabetes mellitus. With the aim to design \u03b1-glucosidase inhibitors with novel chemical scaffolds, three folds ligand and structure based virtual screening was applied. Initially linear quantitative structure activity relationship (QSAR) model was developed by a molecular operating environment (MOE) using a training set of thirty-two known inhibitors, which showed good correlation coefficient (r2 = 0.88), low root mean square error (RMSE = 0.23), and cross-validated correlation coefficient r2 (q2 = 0.71 and RMSE = 0.31). The model was validated by predicting the biological activities of the test set which depicted r2 value of 0.82, indicating the robustness of the model. For virtual screening, compounds were retrieved from zinc is not commercial (ZINC) database and screened by molecular docking. The best docked compounds were chosen to assess their pharmacokinetic behavior. Later, the \u03b1-glucosidase inhibitory potential of the selected compounds was predicted by their mode of binding interactions. The predicted pharmacokinetic profile, docking scores and protein-ligand interactions revealed that eight compounds preferentially target the catalytic site of \u03b1-glucosidase thus exhibit potential \u03b1-glucosidase inhibition in silico. The \u03b1-glucosidase inhibitory activities of those Hits were predicted by QSAR model, which reflect good inhibitory activities of these compounds. These results serve as a guidelines for the rational drug design and development of potential novel anti-diabetic agents.<\/jats:p>","DOI":"10.3390\/ph14050482","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T21:49:21Z","timestamp":1621460961000},"page":"482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Rational Design of Novel Inhibitors of \u03b1-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening"],"prefix":"10.3390","volume":"14","author":[{"given":"Sobia Ahsan","family":"Halim","sequence":"first","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz 616, Nizwa, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaira","family":"Jabeen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government Post-Graduate College for Women, Shadbagh, Lahore 54950, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajmal","family":"Khan","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz 616, Nizwa, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-5942","authenticated-orcid":false,"given":"Ahmed","family":"Al-Harrasi","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz 616, Nizwa, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2017). IDF Diabetes Atlas, International Diabetes Federation. [8th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/2468-8827.184853","article-title":"WHO Global report on diabetes: A summary","volume":"1","author":"Roglic","year":"2016","journal-title":"Int. J. Noncommun. Dis."},{"key":"ref_3","first-page":"61","article-title":"Diabetes mellitus: A review on pathophysiology, current status of oral medica-tions and future perspectives","volume":"55","author":"Okur","year":"2017","journal-title":"Acta Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.2337\/dc16-1728","article-title":"Physical activity\/exercise and diabetes: A position statement of the American Diabetes Association","volume":"39","author":"Colberg","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_5","first-page":"CD005061","article-title":"Alpha-glucosidase inhibitors for pre-vention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of develop-ing type 2 diabetes mellitus","volume":"12","author":"Moelands","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","first-page":"449","article-title":"Antidiabetic agents with \u03b1-glucosidase inhibition and antioxidant capacity from the shoots of Clausena cambodiana Guill","volume":"13","author":"Damsud","year":"2017","journal-title":"Int. J. Agric. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.phytol.2015.08.018","article-title":"Inhibitors of \u03b1-amylase and \u03b1-glucosidase from Andromachia igniaria Humb. & Bonpl","volume":"14","author":"Saltos","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_8","first-page":"83","article-title":"Cerebrovascular Complications of Diabetes: Alpha Glucosidase Inhibitor as Potential Therapy","volume":"48","author":"Patel","year":"2016","journal-title":"Horm. Metab. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fendo.2017.00006","article-title":"Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management","volume":"8","author":"Chaudhury","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1517\/14740338.2013.752813","article-title":"A review of the efficacy and safety of oral antidiabetic drugs","volume":"12","author":"Stein","year":"2013","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1080\/14756366.2017.1368503","article-title":"\u03b1-Glucosidase inhibition by flavonoids: An in vitro and in silico structure\u2013activity relationship study","volume":"32","author":"Freitas","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_12","first-page":"74","article-title":"Network Pharmacology Studies on the Bioactive Compounds and Action Mechanisms of Natural Products for the Treatment of Diabetes Mellitus: A Review","volume":"8","author":"Li","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45578","DOI":"10.1038\/srep45578","article-title":"Synthesis and biological evaluation of novel ursolic acid analogues as potential \u03b1-glucosidase inhibitors","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2174\/1381612822666151125000550","article-title":"Computer aided drug design: Success and limitations","volume":"22","author":"Ahmad","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_15","first-page":"411","article-title":"Application of computational methods for anticancer drug discovery, design, and optimization","volume":"73","year":"2016","journal-title":"Bol. Med. Hosp. Infant. M\u00e9xico"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fchem.2018.00057","article-title":"Computer-Aided Drug Design in Epigenetics","volume":"6","author":"Lu","year":"2018","journal-title":"Front. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103182","DOI":"10.1016\/j.bioorg.2019.103182","article-title":"Synthesis of novel (R)-4-fluorophenyl-1H-1,2,3-triazoles: A new class of \u03b1-glucosidase inhibitors","volume":"91","author":"Avula","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.sajb.2019.05.008","article-title":"New gorgonane sesquiterpenoid from Teucrium mascatense Boiss, as \u03b1-glucosidase inhibitor","volume":"124","author":"Rizvi","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ur Rehman, N., Rafiq, K., Khan, A., Ahsan Halim, S., Ali, L., Al-Saady, N., Hilal Al-Balushi, A., Al-Busaidi, H.K., and Al-Harrasi, A. (2019). \u03b1-Glucosidase Inhibition and Molecular Docking Studies of Natural Bromin-ated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii. Mar. Drugs, 17.","DOI":"10.3390\/md17120666"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/356083a0","article-title":"Assessment of protein models with three-dimensional profiles","volume":"356","author":"Bowie","year":"1992","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jbiosc.2011.08.016","article-title":"Steric hindrance by 2 amino acid residues determines the substrate specificity of isomaltase from Saccharomyces cerevisiae","volume":"112","author":"Yamamoto","year":"2011","journal-title":"J. Biosci. Bioeng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1098\/rstb.2001.1021","article-title":"Zanamivir: From drug design to the clinic","volume":"356","author":"Elliott","year":"2001","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/13423","article-title":"Design of angiotensin converting enzyme inhibitors","volume":"5","author":"Cushman","year":"1999","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7095","DOI":"10.1128\/JVI.79.11.7095-7103.2005","article-title":"Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro","volume":"79","author":"Chen","year":"2005","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Graves, B.J., Hatada, M.H., Miller, J.K., Graves, M.C., Roy, S., Cook, M.C., Krohn, A., Martin, J.A., and Roberts, N.A. (1991). The Three-Dimensional X-Ray Crystal Structure of HIV-1 Protease Complexed with a Hydroxyethylene Inhibitor. Structure and Function of the Aspartic Proteinases, Springer.","DOI":"10.1007\/978-1-4684-6012-4_58"},{"key":"ref_27","first-page":"739","article-title":"Inhibition of epidermal growth factor receptor-associated tyrosine phos-phorylation in human carcinomas with CP-358,774: Dynamics of receptor inhibition in situ and antitumor effects in athymic mice","volume":"291","author":"Pollack","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","first-page":"777","article-title":"Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma 1 supported by the Na-tional Cancer Institute of Canada and the Pat Myhal Fund for Pancreatic Cancer Research. 1","volume":"1","author":"Ng","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1586\/14737140.3.3.269","article-title":"Erlotinib (Tarceva\u00ae): A promising drug targeting epidermal growth fac-tor receptor tyrosine kinase","volume":"3","author":"Bulgaru","year":"2003","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"616","DOI":"10.5414\/CPP41616","article-title":"Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006","volume":"41","author":"Heim","year":"2003","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6388S","DOI":"10.1158\/1078-0432.CCR-040028","article-title":"Kinase Inhibition with BAY 43\u20139006 in Renal Cell Carcinoma","volume":"10","author":"Ahmad","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1158\/0008-5472.CAN-04-1443","article-title":"BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF\/MEK\/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis","volume":"64","author":"Wilhelm","year":"2004","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/sj.onc.1207166","article-title":"Truncated ErbB2 receptor (p95 ErbB2) is regulated by heregulin through hetero-dimer formation with ErbB3 yet remains sensitive to the dual EGFR\/ErbB2 kinase inhibitor GW572016","volume":"23","author":"Xia","year":"2004","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6652","DOI":"10.1158\/0008-5472.CAN-04-1168","article-title":"A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): Relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells","volume":"64","author":"Wood","year":"2004","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1021\/jm981017j","article-title":"The 16, 17-double bond is needed for irreversible inhibition of human cytochrome P45017\u03b1 by abiraterone (17-(3-Pyridyl) androsta-5, 16-dien-3\u03b2-ol) and related steroidal inhibitors","volume":"41","author":"Jarman","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1038\/sj.bjc.6601879","article-title":"Hormonal impact of the 17alpha-hydroxylase\/C (17, 20)-lyase inhibitor abi-raterone acetate (CB7630) in patients with prostatic cancer","volume":"90","author":"Judson","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1016\/j.bmc.2007.10.094","article-title":"Synthesis, biological evaluation and molecular modelling studies of methylene-imidazole substituted biaryls as inhibitors of human 17\u03b1-hydroxylase-17, 20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure","volume":"16","author":"Jagusch","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1056\/NEJMoa1007056","article-title":"Crizotinib inALK-Rearranged Inflammatory Myofibroblastic Tumor","volume":"363","author":"Butrynski","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_39","first-page":"1477","article-title":"Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases","volume":"11","author":"Rodig","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3389\/fphar.2018.01275","article-title":"QSAR-based virtual screening: Advances and applications in drug discovery","volume":"9","author":"Neves","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kwon, S., Bae, H., Jo, J., and Yoon, S. (2019). Comprehensive ensemble in QSAR prediction for drug discovery. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-3135-4"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.bioorg.2018.01.033","article-title":"Synthesis, \u03b1-glucosidase inhibition and molecular docking study of coumarin based derivatives","volume":"77","author":"Taha","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1016\/j.bmcl.2017.05.007","article-title":"Synthesis, biological evaluation and molecular docking studies of chromone hydra-zone derivatives as \u03b1-glucosidase inhibitors","volume":"27","author":"Wang","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14786419.2018.1437427","article-title":"A new sulphated flavone and other phytoconstituents from the leaves of Tetracera indica Merr. and their alpha-glucosidase inhibitory activity","volume":"33","author":"Alhassan","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gong, Z., Peng, Y., Qiu, J., Cao, A., Wang, G., and Peng, Z. (2017). Synthesis, In Vitro \u03b1-Glucosidase Inhibitory Activity and Molecular Docking Studies of Novel Benzothiazole-Triazole Derivatives. Molecules, 22.","DOI":"10.3390\/molecules22091555"},{"key":"ref_46","unstructured":"MOE (2019). Molecular Operating Environment (MOE), 2013.08, Chemical Computing Group."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2014A Free Database of Commercially Available Compounds for Virtual Screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/5\/482\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:43Z","timestamp":1760162623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/5\/482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ph14050482"],"URL":"https:\/\/doi.org\/10.3390\/ph14050482","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]}}}