{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:29:55Z","timestamp":1772087395849,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-13-00029"],"award-info":[{"award-number":["20-13-00029"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>A series of bornyl derivatives of p-(benzyloxy)phenylpropionic acid were prepared, and their hypoglycemic activities were examined by an oral glucose tolerance test in mice. The results of this test revealed two compounds, 1 and 3, that can reduce the blood level of glucose similarly to reference compound vildagliptin. Both compounds were tested in an experiment on mice with metabolic disorders: the C57BL\/6Ay strain. Along with hypoglycemic properties, the two compounds showed different abilities to correct lipid metabolism disorders. In silico prediction revealed that the studied substances are most likely bifunctional multitarget hypoglycemic compounds whose mechanism of action is based on a pronounced reduction in insulin resistance and a strong incretin-mimetic effect. The difference in the size of effects of these compounds on biochemical parameters of blood in the experiment on C57BL\/6Ay mice was in good agreement with the computational prediction of the priority ranking of biological targets for these compounds. These results indicate that bornyl derivatives of p-(benzyloxy)phenylpropionic acid have a good potential as new agents for diabetes mellitus treatment due to their hypoglycemic and lipid-normalizing properties.<\/jats:p>","DOI":"10.3390\/ph13110404","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T06:23:52Z","timestamp":1605767032000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bornyl Derivatives of p-(Benzyloxy)Phenylpropionic Acid: In Vivo Evaluation of Antidiabetic Activity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-7945","authenticated-orcid":false,"given":"Sergey","family":"Kuranov","sequence":"first","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-3453","authenticated-orcid":false,"given":"Olga","family":"Luzina","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-4223","authenticated-orcid":false,"given":"Mikhail","family":"Khvostov","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy","family":"Baev","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darya","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya","family":"Zhukova","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Vassiliev","sequence":"additional","affiliation":[{"name":"Reasearch Center of Innovative Medicines, Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs, Volgograd State Medical University, Ministry of Health of Russian Federation, 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-5052","authenticated-orcid":false,"given":"Andrey","family":"Kochetkov","sequence":"additional","affiliation":[{"name":"Reasearch Center of Innovative Medicines, Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs, Volgograd State Medical University, Ministry of Health of Russian Federation, 400131 Volgograd, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Tolstikova","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nariman","family":"Salakhutdinov","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","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. Non-Commun. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/bja\/85.1.69","article-title":"Insulin: Understanding its action in health and disease","volume":"85","author":"Sonksen","year":"2000","journal-title":"Br. J. Anaesth."},{"key":"ref_3","first-page":"V","article-title":"Is Diabetes Becoming the Biggest Epidemic of the Twenty-first Century?","volume":"1","author":"Tabish","year":"2007","journal-title":"Int. J. Health Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2337\/dci18-0012","article-title":"The Cost of Diabetes Care\u2014An Elephant in the Room","volume":"45","author":"Riddle","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.pcad.2019.08.004","article-title":"Obesity, risk of diabetes and role of physical activity, exercise training and cardiorespiratory fitness","volume":"62","author":"Carbone","year":"2019","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2019). 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2019. Diabetes Care, 42, 90\u2013102.","DOI":"10.2337\/dc19-S009"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vieira, R., Souto, S.B., S\u00e1nchez-L\u00f3pez, E., Machado, A.L., Severino, P., Jose, S., Santini, A., Fortuna, A., Garc\u00eda, M.L., and Silva, A.M. (2019). Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome\u2014Review of Classical and New Compounds: Part-I. Pharmaceuticals, 12.","DOI":"10.3390\/ph12040152"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Habtemariam, S. (2017). Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010004"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.biopha.2017.09.122","article-title":"Ameliorative effect of borneol, a natural bycyclic monoterpene against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic Wistar rats","volume":"96","author":"Kodikonda","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1070\/RCR4624","article-title":"Chemical approach to the design of effective antidiabetic agents","volume":"85","author":"Rogachev","year":"2016","journal-title":"Russ. Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.bmcl.2017.01.034","article-title":"Exploration of phenylpropanoic acids as agonists of the free fatty acid receptor 4 (FFA4): Identification of an orally efficacious FFA4 agonist","volume":"27","author":"Sparks","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hiroyuki, M., and Hashimoto, Y. (2008). Structural development studies of subtype-selective ligands for peroxisome proliferator-activated receptors (PPARs) based on the 3,4-disubstituted phenylpropanoic acid scaffold as a versatile template. PPAR Res., 689859.","DOI":"10.1155\/2008\/689859"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/cmdc.201400007","article-title":"3-Phenylpropanoic acid-based phosphotyrosine (pTyr) mimetics: Hit evolution to a novel orally active protein tyrosine phosphatase 1B (PTP1B) inhibitor","volume":"9","author":"Tang","year":"2014","journal-title":"ChemMedChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103830","DOI":"10.1016\/j.bioorg.2020.103830","article-title":"Exploring bulky natural and natural-like periphery in the design of p-(benzyloxy)phenylpropionic acid agonists of free fatty acid receptor 1 (GPR40)","volume":"99","author":"Kuranov","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.2337\/diaspect.22.2.92","article-title":"New Drugs in Development for the Treatment of Diabetes","volume":"22","author":"Levien","year":"2009","journal-title":"Diabetes Spectrum"},{"key":"ref_17","first-page":"588","article-title":"American Diabetes association\u201470th scientific sessions\u2014Research on novel therapeutics","volume":"13","author":"Croasdell","year":"2010","journal-title":"Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.14341\/DM20151101-109","article-title":"Drug discovery for type 2 diabetes mellitus and metabolic syndrome: Ten novel biological targets","volume":"18","author":"Tyurenkov","year":"2015","journal-title":"Diabetes Mellit."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: A worldwide hub of protein knowledge","volume":"47","author":"Bateman","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/978-94-017-9257-8_12","article-title":"Consensus Drug Design Using IT Microcosm","volume":"Volume 17","author":"Gorb","year":"2014","journal-title":"Application of Computational Techniques in Pharmacy and Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1134\/S0022476619110179","article-title":"Studying dependences between the chemotype structure of some natural compounds and the spectrum of their targeted activities correlated with the hypoglycemic effect","volume":"60","author":"Vasilyev","year":"2019","journal-title":"J. Struct. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kubinyi, H., Folkers, G., and Martin, Y.C. (2002). Similarity and Dissimilarity: A Medicinal Chemist\u2019s View. 3D QSAR in Drug Design. Three-Dimensional Quantitative Structure Activity Relationships, Springer.","DOI":"10.1007\/0-306-46857-3_13"},{"key":"ref_23","unstructured":"(2020, November 17). MarvinSketch, ChemAxon Kft. Available online: http:\/\/www.chemaxon.com\/products\/marvin\/marvinsketch\/."},{"key":"ref_24","unstructured":"MOPAC (2020, November 17). Stewart Computational Chemistry. Available online: http:\/\/openmopac.net."},{"key":"ref_25","first-page":"256","article-title":"Neural network modeling of multitarget RAGE inhibitory activity","volume":"13","author":"Vassiliev","year":"2019","journal-title":"Biochem. Suppl. Ser. B Biomed. Chem."},{"key":"ref_26","unstructured":"(2020, November 17). RCSB PDB, Protein Data Bank. Available online: https:\/\/www.rcsb.org\/."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comp. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.18699\/VJ18.358","article-title":"Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation","volume":"22","author":"Piskunova","year":"2018","journal-title":"Vavilov J. Genet. Breed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrd.2015.4","article-title":"G protein-coupled receptors as targets for anti-diabetic therapeutics","volume":"15","author":"Oh","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.molmet.2015.09.015","article-title":"Incretin-like effects of small molecule trace amine-associated receptor 1 agonists","volume":"5","author":"Raab","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1242\/dmm.006239","article-title":"Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice","volume":"3","author":"Ayala","year":"2010","journal-title":"Dis. Model. Mech."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/713609354","article-title":"Dipeptidyl-Peptidase IV from Bench to Bedside: An Update on Structural Properties, Functions, and Clinical Aspects of the Enzyme DPP IV","volume":"40","author":"Lambeir","year":"2003","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1124\/jpet.105.087064","article-title":"Acute and Chronic Effects of the Incretin Enhancer Vildagliptin in Insulin-Resistant Rats","volume":"315","author":"Burkey","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1071\/CH9841785","article-title":"The endo\u2014And exo 1,7,7-Trimethylbicyclo[2.2.1]heptan- 2-amines (Bornan-2-amines) and their acetamides","volume":"37","author":"Carman","year":"1984","journal-title":"Aust. J. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.2337\/diacare.17.2.152","article-title":"A Mathematical Model for the Determination of Total Area under Glucose Tolerance and Other Metabolic Curves","volume":"17","author":"Tai","year":"1994","journal-title":"Diabetes Care"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:34:18Z","timestamp":1760178858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ph13110404"],"URL":"https:\/\/doi.org\/10.3390\/ph13110404","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]}}}