{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T23:56:43Z","timestamp":1772150203445,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP19578051"],"award-info":[{"award-number":["AP19578051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study presents the synthesis and antidiabetic and hematopoietic activity of ionic compounds based on 2-(diphenylmethoxy)-N,N-dimethylethanamine (diphenhydramine). Synthesis is carried out under ultrasonic (US) and microwave (MW) irradiation as well as using a conventional method (thermal activation). The synthesized ionic compounds have been tested for antidiabetic effect according to the inhibitory action against \u03b1-glucosidase and \u03b1-amylase (in vitro). All the synthesized derivatives of diphenhydramine showed higher inhibitory activity against \u03b1-glucosidase than commercially available diphenhydramine hydrochloride. Moreover, two of them, 1m (66.9%) and 1k (64.2%), had a greater inhibitory activity than the reference drug acarbose (51.8%). The hematopoietic activity was studied in albino laboratory female rats (in vivo). The compounds 1b, 1f, and 1k can restore immune blood cells (hematopoietic activity), equal to or exceeding that of the commercially available diphenhydramine hydrochloride and control (methyluracil).<\/jats:p>","DOI":"10.3390\/molecules30142967","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"2967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ultrasound and Microwave-Assisted Synthesis and Antidiabetic and Hematopoietic Activity of Diphenhydramine Derivatives"],"prefix":"10.3390","volume":"30","author":[{"given":"Anuar","family":"Dauletbakov","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7418-0564","authenticated-orcid":false,"given":"Yelizaveta","family":"Belyankova","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-5276","authenticated-orcid":false,"given":"Saniya","family":"Assylbekova","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-2616","authenticated-orcid":false,"given":"Darya","family":"Zolotareva","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Bayazit","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Layilya","family":"Baktybayeva","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, al-Farabi Ave, 71, Almaty 050040, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2537-1559","authenticated-orcid":false,"given":"Ulan","family":"Kemelbekov","sequence":"additional","affiliation":[{"name":"Pharmacy Scientific Research Center, South Kazakhstan Medical Academy, 1 Al-Farabi Square, Shymkent 160019, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-707X","authenticated-orcid":false,"given":"Valentina","family":"Yu","sequence":"additional","affiliation":[{"name":"JCS \u00abA.B. Bekturov Institute of Chemical Sciences\u00bb, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1618-900X","authenticated-orcid":false,"given":"Nailya","family":"Ibragimova","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs, Laboratory of Pharmacology and Toxicology, Auezov Str., 84, Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Zazybin","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Kazakh-British Technical University, 59 Tole bi Str., Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","unstructured":"Capelo-Martinez, J.-L. (2009). Ultrasounds in Chemistry: Analytical Applications, Wiley."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1002\/anie.200400655","article-title":"Controlled Microwave Heating in Modern Organic Synthesis","volume":"43","author":"Kappe","year":"2004","journal-title":"Angew. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.ultsonch.2007.10.009","article-title":"Improved extraction of vegetable oils under high-intensity ultrasound and\/or microwaves","volume":"15","author":"Cravotto","year":"2008","journal-title":"Ultrason. Sonochem."},{"key":"ref_4","first-page":"46","article-title":"Comparison of Conventional and Microwave-assisted Synthesis of Benzotriazole Derivatives","volume":"76","author":"Shah","year":"2014","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0040-4039(00)83996-9","article-title":"The use of microwave ovens for rapid organic synthesis","volume":"27","author":"Gedye","year":"1986","journal-title":"Tetrahedron Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1126\/science.247.4949.1439","article-title":"Sonochemistry","volume":"247","author":"Suslick","year":"1990","journal-title":"Science"},{"key":"ref_7","unstructured":"(2025, March 11). IDF Diabetes Atlas, Available online: https:\/\/diabetesatlas.org\/idfawp\/resource-files\/2010\/07\/IDF_diabetes_atlas_sixth_edition_en.pdf."},{"key":"ref_8","first-page":"545","article-title":"New strategy in type 2 diabetes tested in clinical trials: Glucagon-like peptide 1 (GLP-1) affects basic caused of the disease","volume":"102","author":"Ahren","year":"2005","journal-title":"Lakartidningen"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.2337\/diacare.28.8.1936","article-title":"Improved meal-related (beta)-cell function and insulin sensitivity by the dipeptidyl peptidase-iv inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year","volume":"28","author":"Ahren","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1001\/jama.298.2.194","article-title":"Efficacy and safety of incretin therapy in type 2 diabetes: Systemic review and meta-analysis","volume":"298","author":"Amori","year":"2007","journal-title":"JAMA"},{"key":"ref_11","first-page":"451","article-title":"Animal models in type 2 diabetes research: An overview","volume":"125","author":"Srinivasan","year":"2007","journal-title":"Indian J. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0168-8227(02)00103-1","article-title":"Models of pancreatic regeneration in diabetes","volume":"58","author":"Risbud","year":"2002","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.4049\/jimmunol.138.10.3224","article-title":"Effect of immunodeficiency on diabetogenesis in getenocally diabetic (db\/db) mice","volume":"138","author":"Leiter","year":"1987","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pliszka, M., and Szablewski, L. (2024). Associations between Diabetes Mellitus and Selected Cancers. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137476"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1008862","article-title":"Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death","volume":"364","author":"Kaptoge","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1001\/jama.2008.824","article-title":"Long-Term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"300","author":"Barone","year":"2008","journal-title":"JAMA"},{"key":"ref_17","first-page":"37","article-title":"Diphenhydramine as an alternative local anesthetic agent","volume":"2","author":"Pavlidakey","year":"2009","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00204-011-0659-4","article-title":"Genotoxicity and carcinogenicity studies of antihistamines","volume":"85","author":"Brambilla","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12823","DOI":"10.1002\/slct.202001771","article-title":"Synthesis and Ecotoxicological Studies of ionic compounds based on Tolperisone, Diphenhydramine and Trimecaine","volume":"5","author":"Giner","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.26452\/ijrps.v11i4.3102","article-title":"Anti-diabetic activity of diphenhydramine in diabetic rats","volume":"11","author":"Chayng","year":"2020","journal-title":"Int. J. Res. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.4103\/0253-7613.161270","article-title":"In-vitro \u03b1-amylase and \u03b1-glucosidase inhibitory activity of Adiantum caudatum Linn. and Celosia argentea Linn. extracts and fractions","volume":"47","author":"Telagari","year":"2015","journal-title":"Indian J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1590\/fst.08420","article-title":"Inhibitory effects of l-3-phenyllacitc acid on the activity of mushnroom pholyphenol oxidase","volume":"41","author":"Haiwei","year":"2021","journal-title":"Food Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bernfeld, P., Colowick, S.P., and Kaplan, N.O. (1955). Amylase, \u03b1 and \u03b2. Methods in Enzymology, Academic Press.","DOI":"10.1016\/0076-6879(55)01021-5"},{"key":"ref_24","unstructured":"PASS Online (2025, April 08). Way2Drug Predictive Service. Available online: https:\/\/www.way2drug.com\/passonline\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.51580\/2022-3\/2710-1185.82","article-title":"Synthesis and growth-stimulating activity of trimecaine ethyl iodoethanoate","volume":"3","author":"Dauletbakov","year":"2022","journal-title":"Chem. J. Kaz."},{"key":"ref_26","first-page":"308","article-title":"Eine Vereinfachung und Vervollkommnung meiner Methylenazur-Methylenblau-Eosin-F\u00e4rbemethode zur Erzielung der Romanowsky-Nochtschen Chromatinf\u00e4rbung","volume":"37","author":"Giemsa","year":"1904","journal-title":"Cent. Bakt."},{"key":"ref_27","unstructured":"Order of the Minister of Healthcare of the Republic of Kazakhstan No. KR DSM-181\/2020 of 4 November 2020 (2025, March 11). On approval of the Rules for the Assessment of Materials and Compliance of Preclinical (non-clinical) Studies with Good Laboratory Practice (GLP) Requirements of the Republic of Kazakhstan and\/or the Eurasian Economic Union within the Framework of Pharmaceutical Inspection. (Registered with the Ministry of Justice of the Republic of Kazakhstan on 5 November 2020 under No. 21596). Available online: https:\/\/adilet.zan.kz\/eng\/docs\/V2000021596."},{"key":"ref_28","unstructured":"(2025, May 13). RCSB Protein Data Bank (RCSB PDB). Available online: https:\/\/www.rcsb.org\/."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/14\/2967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:49Z","timestamp":1760033389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/14\/2967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":28,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["molecules30142967"],"URL":"https:\/\/doi.org\/10.3390\/molecules30142967","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,15]]}}}