{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:29:53Z","timestamp":1790886593320,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research, Najran University, Najran, Saudi Arabia","award":["NU\/MID\/17\/091"],"award-info":[{"award-number":["NU\/MID\/17\/091"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The Food and Drug Administration (FDA) approved a new class of anti-diabetic medication (a sodium\u2013glucose co-transporter 2 (SGLT2) inhibitor) in 2013. However, SGLT2 inhibitor drugs are under evaluation due to their associative side effects, such as urinary tract and genital infection, urinary discomfort, diabetic ketosis, and kidney problems. Even clinicians have difficulty in recommending it to diabetic patients due to the increased probability of urinary tract infection. In our study, we selected natural SGLT2 inhibitors, namely acerogenin B, formononetin, (\u2212)-kurarinone, (+)-pteryxin, and quinidine, to explore their potential against an emerging uropathogenic bacterial therapeutic target, i.e., FimH. FimH plays a critical role in the colonization of uropathogenic bacteria on the urinary tract surface. Thus, FimH antagonists show promising effects against uropathogenic bacterial strains via their targeting of FimH\u2019s adherence mechanism with less chance of resistance. The molecular docking results showed that, among natural SGLT2 inhibitors, formononetin, (+)-pteryxin, and quinidine have a strong interaction with FimH proteins, with binding energy (\u2206G) and inhibition constant (ki) values of \u22125.65 kcal\/mol and 71.95 \u00b5M, \u22125.50 kcal\/mol and 92.97 \u00b5M, and \u22125.70 kcal\/mol and 66.40 \u00b5M, respectively. These interactions were better than those of the positive control heptyl \u03b1-d-mannopyranoside and far better than those of the SGLT2 inhibitor drug canagliflozin. Furthermore, a 50 ns molecular dynamics simulation was conducted to optimize the interaction, and the resulting complexes were found to be stable. Physicochemical property assessments predicted little toxicity and good drug-likeness properties for these three compounds. Therefore, formononetin, (+)-pteryxin, and quinidine can be proposed as promising SGLT2 inhibitors drugs, with add-on FimH inhibition potential that might reduce the probability of uropathogenic side effects.<\/jats:p>","DOI":"10.3390\/molecules26030582","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T11:13:53Z","timestamp":1611314033000},"page":"582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Biocomputational Prediction Approach Targeting FimH by Natural SGLT2 Inhibitors: A Possible Way to Overcome the Uropathogenic Effect of SGLT2 Inhibitor Drugs"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-296X","authenticated-orcid":false,"given":"Mutaib M.","family":"Mashraqi","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4265-9255","authenticated-orcid":false,"given":"Navaneet","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Biomolecular Engineering Laboratory, School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India"},{"name":"Department of Molecular and Cell Biology, Leicester Institute of Structural and Chemical Biology, University of Leicester Henry Wellcome Building, Lancaster Road Leicester, Leicester LE1 7HB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qamre","family":"Alam","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Alshamrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mosa M.","family":"Bahnass","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia"},{"name":"Department of Animal Medicine (Infectious Diseases), Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-8445","authenticated-orcid":false,"given":"Khurshid","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-9451","authenticated-orcid":false,"given":"Amany I.","family":"Alqosaibi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-3996","authenticated-orcid":false,"given":"Mashael M.","family":"Alnamshan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Sayeed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirza Masroor Ali","family":"Beg","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Mishra","sequence":"additional","affiliation":[{"name":"Biomolecular Engineering Laboratory, School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibhghatulla","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Mohd Danish","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Hail, P.O. Box 2440, Hail 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2337\/dc14-1453","article-title":"Life years lost and lifetime health care expenditures associated with diabetes in the U.S., national health interview survey, 1997\u20132000","volume":"38","author":"Leung","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.2337\/diacare.26.2.510","article-title":"Quantifying the risk of infectious diseases for people with diabetes","volume":"26","author":"Shah","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1086\/427699","article-title":"Diabetes mellitus as a risk and prognostic factor for community-acquired bacteremia due to enterobacteria: A 10-year, population-based study among adults","volume":"40","author":"Thomsen","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2337\/diacare.27.1.70","article-title":"Diabetes and outcome of community-acquired pneumococcal bacteremia: A 10-year population based cohort study","volume":"27","author":"Thomsen","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bcp.2015.09.005","article-title":"SGLT2 inhibitors","volume":"101","author":"Dardi","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00125-006-0570-3","article-title":"Influence of diabetes and hyperglycaemia on infectious disease hospitalization and outcome","volume":"50","author":"Benfield","year":"2007","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/oxfordjournals.aje.a000181","article-title":"Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women","volume":"161","author":"Boyko","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.diabres.2013.12.052","article-title":"Genital and urinary tract infections in diabetes: Impact of pharmacologically induced glucosuria","volume":"103","author":"Geerlings","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_9","unstructured":"U.S. Food and Drug Administration (2016, November 10). FDA Drug Safety Communication: FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections, Available online: http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm475463.htm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1038\/emboj.2008.155","article-title":"Architectures and biogenesis of non-flagellar protein appendages in Gram-negative bacteria","volume":"27","author":"Fronzes","year":"2008","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1517\/13543776.2016.1131266","article-title":"Mannose-derived FimH antagonists: A promising anti-virulence therapeutic strategy for urinary tract infections and Crohn\u2019s disease","volume":"26","author":"Cusumano","year":"2016","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1021\/np9007987","article-title":"Gneyulins A and B, stilbene trimers, and noidesols A and B, dihydroflavonol-C-glucosides, from the bark of Gnetum gnemonoides","volume":"73","author":"Shimokawa","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1016\/j.bmc.2007.03.011","article-title":"Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens","volume":"15","author":"Sato","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e00504","DOI":"10.1002\/prp2.504","article-title":"Novel natural and synthetic inhibitors of solute carriers SGLT1 and SGLT2","volume":"7","author":"Oranje","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.mimet.2010.06.015","article-title":"Development of an Aggregation Assay to Screen FimH Antagonists","volume":"82","author":"Abgottspon","year":"2010","journal-title":"J. Microbiol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1023\/A:1020444330011","article-title":"Rate-limited steps of human oral absorption and QSAR studies","volume":"19","author":"Zhao","year":"2002","journal-title":"Pharm. Res."},{"key":"ref_20","first-page":"831","article-title":"simple click by click protocol to perform docking: AutoDock 4.2 made easy for non-bioinformaticians","volume":"12","author":"Rizvi","year":"2013","journal-title":"EXCLI J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, flexible, and free","volume":"26","author":"Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","author":"Pronk","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/jcc.20090","article-title":"A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6","volume":"25","author":"Oostenbrink","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1103\/PhysRevB.31.2643","article-title":"Molecular-dynamics study of atomic motions in water","volume":"31","author":"Toukan","year":"1985","journal-title":"Phys. Rev. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: A linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A tool for high-throughput crystallography of protein-ligand complexes","volume":"60","year":"2004","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"897296","DOI":"10.1155\/2014\/897296","article-title":"Psoraleacorylifolia L. seed extract ameliorates streptozotocin-induced diabetes in mice by inhibition of oxidative stress","volume":"2014","author":"Seo","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1093\/jn\/137.10.2196","article-title":"Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans","volume":"137","author":"Monteiro","year":"2007","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.phytochem.2006.12.015","article-title":"alpha-Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae)","volume":"68","author":"Mbaze","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jep.2005.04.007","article-title":"Antidiabetic activity and toxicity of Zizyphus spina-christi leaves","volume":"101","author":"Salim","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: A powerful approach for structure-based drug discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Udrescu, L., Bogdan, P., Chi\u015f, A., S\u00eerbu, I.O., Top\u00eerceanu, A., V\u0103ru\u0163, R.M., and Udrescu, M. (2020). Uncovering New Drug Properties in Target-Based Drug-Drug Similarity Networks. Pharmaceutics, 12.","DOI":"10.1101\/2020.03.12.988600"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pinzi, L., and Rastelli, G. (2019). Molecular Docking: Shifting Paradigms in Drug Discovery. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184331"},{"key":"ref_35","first-page":"139","article-title":"Sodium Glucose Co transporter 2 (SGLT2) Inhibitors: A New Sword for the Treatment of Type 2 Diabetes Mellitus","volume":"1","author":"Rajesh","year":"2010","journal-title":"Int. J. Pharma Sci. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/bab.1319","article-title":"Forxiga (Dapagliflozin): Plausible role in the treatment of diabetes associated neurological disorders","volume":"63","author":"Shaikh","year":"2016","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2174\/18715273113126660160","article-title":"Invokana (Canagliflozin) as a Dual Inhibitor of Acetylcholinesterase and Sodium Glucose Co-Transporter 2: Advancement in Alzheimer\u2019s Disease-Diabetes Type 2 Linkage via an Enzoinformatics Study","volume":"13","author":"Rizvi","year":"2014","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/1947-2714.128471","article-title":"Canagliflozin: A novel SGLT2 inhibitor for Type 2 Diabetes Mellitus","volume":"6","author":"Kaushal","year":"2014","journal-title":"N. Am. J. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7975","DOI":"10.1074\/jbc.M110.187880","article-title":"Sugar binding residue affects apparent Na affinity and transport stoichiometry in mouse sodium\/glucose cotransporter type 3B","volume":"286","author":"Barcelona","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.bpj.2008.09.045","article-title":"Effects on conformational states of the rabbit sodium\/glucose cotransporter through modulation of polarity and charge at glutamine 457","volume":"96","author":"Liu","year":"2009","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1385\/CBB:36:2-3:115","article-title":"Molecular basis for glucose galactose malabsorption","volume":"36","author":"Wright","year":"2002","journal-title":"Cell Biochem. Biophys."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Choi, C.I. (2016). Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents. Molecules, 21.","DOI":"10.3390\/molecules21091136"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e13642","DOI":"10.14814\/phy2.13642","article-title":"Metabolic effects of tofogliflozin are efficiently enhanced with appropriate dietary carbohydrate ratio and are distinct from carbohydrate restriction","volume":"6","author":"Ito","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.bbrc.2015.10.109","article-title":"Protective effects of SGLT2 inhibitor Luseogliflozin on pancreatic \u03b2-cells in obese type 2 diabetic db\/db mice","volume":"470","author":"Okauchi","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1016\/j.bmc.2010.01.077","article-title":"Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter","volume":"18","author":"Arai","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ddr.21233","article-title":"Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter","volume":"76","author":"Qu","year":"2015","journal-title":"Drug Dev. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1016\/j.bmcl.2016.03.065","article-title":"Modification on the O-glucoside of Sergliflozin-A: A new strategy for SGLT2 inhibitor design","volume":"26","author":"Cao","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1111\/ijcp.12322","article-title":"Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: A randomized trial","volume":"67","author":"Wilding","year":"2013","journal-title":"Int. J. Clin. Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.2337\/dc13-3055","article-title":"Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes","volume":"37","author":"Rosenstock","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"740","DOI":"10.2337\/dc13-0467","article-title":"Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: A 24-Week, multicenter, randomized, double blind, placebo-controlled study","volume":"37","author":"Jabbour","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/dom.12428","article-title":"Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55\u201380 years with type 2 diabetes","volume":"17","author":"Bode","year":"2015","journal-title":"Diabetes Obes. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.diabres.2015.05.044","article-title":"Empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes","volume":"110","author":"Haering","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0924-8579(01)00303-X","article-title":"Urinary tract infection in adults: Research priorities and strategies","volume":"17","author":"Ronald","year":"2001","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1126\/science.1084550","article-title":"Intracellular bacterial biofilm-like pods in urinary tract infections","volume":"301","author":"Anderson","year":"2003","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1080\/17460441.2017.1331216","article-title":"Rational Design Strategies for FimH Antagonists: New Drugs on the Horizon for Urinary Tract Infection and Crohn\u2019s Disease","volume":"12","author":"Hannan","year":"2017","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wellens, A., Garofalo, C., Nguyen, H., Van Gerven, N., Sl\u00e4tteg\u00e5rd, R., Hernalsteens, J.P., Wyns, L., Oscarson, S., De Greve, H., and Hultgren, S. (2008). Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex. PLoS ONE, 3.","DOI":"10.1371\/annotation\/ea59d179-0a71-4836-86f0-8d375f5df089"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1046\/j.1365-2958.2002.02915.x","article-title":"Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection","volume":"44","author":"Hung","year":"2002","journal-title":"J. Mol. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"22439","DOI":"10.1073\/pnas.0902179106","article-title":"Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mousavifar, L., Vergoten, G., Charron, G., and Roy, R. (2019). Comparative study of aryl O-, C-, and S-mannopyranosides as potential adhesion inhibitors toward uropathogenic E. coli FimH. Molecules, 24.","DOI":"10.3390\/molecules24193566"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1021\/acs.accounts.8b00397","article-title":"Development of mannopyranoside therapeutics against adherent-invasive Escherichia coli infections","volume":"51","author":"Mousavifar","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sarshar, M., Behzadi, P., Ambrosi, C., Zagaglia, C., Palamara, A.T., and Scribano, D. (2020). FimH and anti-adhesive therapeutics: A disarming strategy against uropathogens. Antibiotics, 9.","DOI":"10.3390\/antibiotics9070397"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2478\/acph-2018-0004","article-title":"Effective anti-adhesives of uropathogenic Escherichia coli","volume":"68","author":"Neuberg","year":"2018","journal-title":"Acta Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1021\/acs.jafc.5b03030","article-title":"In vivo consumption of cranberry exerts ex vivo antiadhesive activity against FimH-Dominated uropathogenic Escherichia coli: A combined in vivo, ex vivo, and in vitro study of an extract from vaccinium macrocarpon","volume":"63","author":"Rafsanjany","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s12539-013-0202-9","article-title":"An enzoinformatics study for prediction of efficacies of three novel penem antibiotics against New Delhi metallo-\u03b2-lactamase-1 bacterial enzyme","volume":"6","author":"Ansari","year":"2014","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jmgm.2017.04.014","article-title":"The effect of \u03b2-glucan and its potential analog on the structure of Dectin-1 receptor","volume":"74","author":"Chaturvedi","year":"2017","journal-title":"J. Mol. Graph. Model"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4103\/0973-1296.127333","article-title":"An enzoinformatics study targeting polo-like kinases-1 enzyme: Comparative assessment of anticancer potential of compounds isolated from leaves of Ageratum houstonianum","volume":"10","author":"Rizvi","year":"2014","journal-title":"Pharmacogn. Mag."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"18","DOI":"10.4103\/0973-1296.126653","article-title":"Compounds isolated from Ageratum houstonianum inhibit the activity of matrix metalloproteinases (MMP-2 and MMP-9): An oncoinformatics study","volume":"10","author":"Verma","year":"2014","journal-title":"Pharmacogn. Mag."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.2337\/dc15-1251","article-title":"Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program","volume":"38","author":"Erondu","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.bpj.2009.11.011","article-title":"Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors","volume":"98","author":"Kuzmanic","year":"2010","journal-title":"Biophys. J."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/3\/582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:14:04Z","timestamp":1760159644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/3\/582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,22]]},"references-count":69,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["molecules26030582"],"URL":"https:\/\/doi.org\/10.3390\/molecules26030582","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,22]]}}}