{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:35:49Z","timestamp":1768588549387,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tec-nol\u00f3gico"},{"DOI":"10.13039\/501100002322","name":"(CAPES)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o Cearense de Apoio ao Desenvolvimento Cient\u00edfico e Tecno-logico"},{"name":"CAPES\/PPG-Pharmacology UFC","award":["N\u00ba 88887.667396\/2022-00; 2020\u20132024"],"award-info":[{"award-number":["N\u00ba 88887.667396\/2022-00; 2020\u20132024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia, insulin resistance, low-grade inflammation, and oxidative stress that drive cardiometabolic and renal damage despite current therapies. Sodium\u2013glucose cotransporter (SGLT) inhibitors have reshaped the treatment landscape, but residual risk and safety concerns highlight the need for new agents that combine glucose-lowering efficacy with redox\u2013inflammatory modulation. LASSBio-1986 is a synthetic N-acylhydrazone (NAH) derivative designed as a gliflozin-like scaffold with the potential to interact with SGLT1\/2 while also influencing oxidative and inflammatory pathways. Here, we integrated in silico and in vivo approaches to characterize LASSBio-1986 as a multifunctional antidiabetic lead in murine models of glucose dysregulation. PASS and target class prediction suggested a broad activity spectrum and highlighted transporter- and stress-related pathways. Molecular docking indicated high-affinity binding to both SGLT1 and SGLT2, with a modest energetic preference for SGLT2, and ADME\/Tox predictions supported favorable oral drug-likeness. In vivo, intraperitoneal LASSBio-1986 improved oral glucose tolerance and reduced glycemic excursions in an acute glucose challenge model in C57BL\/6 mice, while enhancing hepatic and skeletal muscle glycogen stores. In a dexamethasone-induced insulin-resistance model, LASSBio-1986 improved insulin sensitivity, favorably modulated serum lipids, attenuated thiobarbituric acid-reactive substances (TBARS), restored reduced glutathione (GSH) levels, and rebalanced pro- and anti-inflammatory cytokines in metabolic tissues, with efficacy broadly comparable to dapagliflozin. These convergent findings support LASSBio-1986 as a preclinical, multimodal lead that targets SGLT-dependent glucose handling while mitigating oxidative and inflammatory stress in models relevant to T2DM. Chronic disease models, formal toxicology, and pharmacokinetic studies, particularly with oral dosing, will be essential to define its translational potential.<\/jats:p>","DOI":"10.3390\/ijms27020829","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:04:22Z","timestamp":1768392262000},"page":"829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LASSBio-1986 as a Multifunctional Antidiabetic Lead: SGLT1\/2 Docking, Redox\u2013Inflammatory Modulation and Metabolic Benefits in C57BL\/6 Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Landerson Lopes","family":"Pereira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4078-1417","authenticated-orcid":false,"given":"Raimundo Rigoberto B. Xavier","family":"Filho","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Ara\u00fajo","family":"Freire","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio Bruno Rodrigues","family":"Martins","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maur\u00edcio Gabriel Barros","family":"Perote","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cibelly Loryn Martins","family":"Campos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel Carlos Serrazul","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-8761","authenticated-orcid":false,"given":"Isabelle de F\u00e1tima Vieira Camelo","family":"Maia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Farmacologia da Inflama\u00e7\u00e3o e do C\u00e2ncer (LAFICA), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata Barbosa","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Instituto de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Serop\u00e9dica CEP 23890-000, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-2879","authenticated-orcid":false,"given":"Luis Gabriel Valdivieso","family":"Gelves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro CEP 21941-590, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-8228","authenticated-orcid":false,"given":"Dami\u00e3o Sampaio de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4148-3777","authenticated-orcid":false,"given":"R\u00e9gia Karen Barbosa De","family":"Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-4340","authenticated-orcid":false,"given":"Paulo Iury Gomes","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago Lima","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Universidade Federal do Cear\u00e1, Fortaleza CEP 60430-160, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-5148","authenticated-orcid":false,"given":"Gisele Silvestre","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9741-7560","authenticated-orcid":false,"given":"Deysi Viviana Tenazoa","family":"Wong","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Farmacologia da Inflama\u00e7\u00e3o e do C\u00e2ncer (LAFICA), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-6351","authenticated-orcid":false,"given":"Lidia Moreira","family":"Lima","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro CEP 21941-590, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter Jos\u00e9","family":"Pel\u00e1ez","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones em Fisicoqu\u00edmica de C\u00f3rdoba (INFIQC), C\u00f3rdoba X5000HUA, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcia Machado","family":"Marinho","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-164X","authenticated-orcid":false,"given":"H\u00e9lcio Silva dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane Eire Silva Alencar de","family":"Menezes","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-8775","authenticated-orcid":false,"given":"Emmanuel Silva","family":"Marinho","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-6125","authenticated-orcid":false,"given":"Kirley Marques","family":"Canuto","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Naturais, Universidade Estadual do Cear\u00e1, Av. Dr. Silas Munguba, 1700, Fortaleza CEP 60714-903, Cear\u00e1, Brazil"},{"name":"Embrapa Agroind\u00fastria Tropical, Rua Dra, Sara Mesquita, 2270-Pici, Fortaleza CEP 60020-181, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-4434","authenticated-orcid":false,"given":"Pedro Filho Noronha","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacogenetics, Center for Drug Research and Development (NPDM), Universidade Federal do Cear\u00e1, Fortaleza CEP 60355-636, Cear\u00e1, Brazil"},{"name":"Laboratory of Bioinformatics Applied to Human Health, Department of Pathology and Legal Medicine, Universidade Federal do Cear\u00e1, Fortaleza CEP 60355-636, Cear\u00e1, Brazil"},{"name":"National Institute of Science and Technology in Human Pathogenic Fungi (FunVir), Ribeir\u00e3o Preto CEP 14040-903, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francimauro Sousa","family":"Morais","sequence":"additional","affiliation":[{"name":"Instituto Federal do Amazonas-Campus Manaus Centro Av. Sete de Setembro, 1975. Centro, Manaus CEP 69020-120, Amazonas, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nylane Maria Nunes de","family":"Alencar","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8254-4727","authenticated-orcid":false,"given":"Marisa Jadna Silva","family":"Frederico","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Farmacologia (LFB), Departamento de Farmacologia e Fisiologia, N\u00facleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Faculdade de Medicina, Universidade Federal do Cear\u00e1, Rua Coronel Nunes de Melo, 1000-Rodolfo Te\u00f3filo, Fortaleza CEP 60430-275, Cear\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11623","DOI":"10.1038\/s41598-024-62122-y","article-title":"Lifestyle and Metabolic Risk Factors, and Diabetes Mellitus Prevalence in European Countries from Three Waves of the European Health Interview Survey","volume":"14","author":"Shahin","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bellou, V., Belbasis, L., Tzoulaki, I., and Evangelou, E. (2018). Risk Factors for Type 2 Diabetes Mellitus: An Exposure-Wide Umbrella Review of Meta-Analyses. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194127"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., and Weiskirchen, R. (2024). The Role of Obesity in Type 2 Diabetes Mellitus\u2014An Overview. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031882"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Weinberg Sibony, R., Segev, O., Dor, S., and Raz, I. (2023). Drug Therapies for Diabetes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417147"},{"key":"ref_5","first-page":"102037","article-title":"Type 2 Diabetes Mellitus\u2014Conventional Therapies and Future Perspectives in Innovative Treatment","volume":"42","author":"Gieroba","year":"2025","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrendo.2016.86","article-title":"Pharmacology and Therapeutic Implications of Current Drugs for Type 2 Diabetes Mellitus","volume":"12","author":"Tahrani","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s13300-025-01751-6","article-title":"Time to Treatment Intensification with Glucagon-Like Peptide-1 Receptor Agonists Versus Comparators in People with Type 2 Diabetes Treated with Metformin","volume":"16","author":"Ostrominski","year":"2025","journal-title":"Diabetes Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.4093\/dmj.2024.0660","article-title":"Initial Pharmacological Strategies in People with Early Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis","volume":"49","author":"Choi","year":"2025","journal-title":"Diabetes Metab. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tentolouris, A., Vlachakis, P., Tzeravini, E., Eleftheriadou, I., and Tentolouris, N. (2019). SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16162965"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCULATIONAHA.116.021887","article-title":"Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus","volume":"134","author":"Heerspink","year":"2016","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ckj\/sfaa198","article-title":"SGLT2 Inhibitors for Non-Diabetic Kidney Disease: Drugs to Treat CKD That Also Improve Glycaemia","volume":"13","author":"Sarafidis","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2147\/DMSO.S233538","article-title":"Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence","volume":"13","author":"Bonora","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mascolo, A., Di Napoli, R., Balzano, N., Cappetta, D., Urbanek, K., De Angelis, A., Scisciola, L., Di Meo, I., Sullo, M.G., and Rafaniello, C. (2022). Safety Profile of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: A Brief Summary. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1010693"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mateoc, T., Dumitrascu, A.-L., Flangea, C., Puscasiu, D., Vlad, T., Popescu, R., Marina, C., and Vlad, D.-C. (2025). SGLT2 Inhibitors: From Structure\u2013Effect Relationship to Pharmacological Response. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146937"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2042098621989134","DOI":"10.1177\/2042098621989134","article-title":"Adverse Events Associated with Sodium Glucose Co-Transporter 2 Inhibitors: An Overview of Quantitative Systematic Reviews","volume":"12","author":"Pelletier","year":"2021","journal-title":"Ther. Adv. Drug Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1016\/j.amjcard.2019.10.029","article-title":"Safety of Sodium-Glucose Co-Transporter 2 Inhibitors","volume":"124","author":"McGill","year":"2019","journal-title":"Am. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14791641211011016","DOI":"10.1177\/14791641211011016","article-title":"Safety of Four SGLT2 Inhibitors in Three Chronic Diseases: A Meta-Analysis of Large Randomized Trials of SGLT2 Inhibitors","volume":"18","author":"Qiu","year":"2021","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Socea, L.-I., Barbuceanu, S.-F., Pahontu, E.M., Dumitru, A.-C., Nitulescu, G.M., Sfetea, R.C., and Apostol, T.-V. (2022). Acylhydrazones and Their Biological Activity: A Review. Molecules, 27.","DOI":"10.3390\/molecules27248719"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1016\/j.bmcl.2018.07.015","article-title":"N-Acylhydrazones as Drugs","volume":"28","author":"Thota","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejmech.2018.01.066","article-title":"Design, Synthesis and Pharmacological Evaluation of N-Benzyl-Piperidinyl-Aryl-Acylhydrazone Derivatives as Donepezil Hybrids: Discovery of Novel Multi-Target Anti-Alzheimer Prototype Drug Candidates","volume":"147","author":"Castelli","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2200548","DOI":"10.1002\/ardp.202200548","article-title":"Anticancer Agents Incorporating the N-acylhydrazone Scaffold: Progress from 2017 to Present","volume":"356","author":"Kassab","year":"2023","journal-title":"Arch. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2174\/0113816128282470240117072322","article-title":"N-Acylhydrazone Pharmacophore\u2019s Analgesic and Anti-Inflammatory Profile: Recent Advancements during the Past Ten Years","volume":"30","author":"Kassab","year":"2024","journal-title":"Curr. Pharm. Des."},{"key":"ref_23","first-page":"e01463","article-title":"In Silico Studies and Antimicrobial Investigation of Synthesised Novel N-Acylhydrazone Derivatives of Indole","volume":"19","author":"Yeye","year":"2023","journal-title":"Sci. Afr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"da Costa Salom\u00e9, D., de Freitas, R.H.C.N., Fraga, C.A.M., and Fernandes, P.D. (2022). Novel Regioisomeric Analogues of Naphthyl-N-Acylhydrazone Derivatives and Their Anti-Inflammatory Effects. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202210.0216.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12439","DOI":"10.1021\/acs.jmedchem.4c01242","article-title":"Development of Novel N -Acylhydrazone Derivatives with High Anti-Obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group","volume":"67","author":"Jiang","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mikus, J., \u015awi\u0105tek, P., Przyby\u0142a, P., Krzy\u017cak, E., Marciniak, A., Kotynia, A., Redzicka, A., Wiatrak, B., Jawie\u0144, P., and G\u0119barowski, T. (2023). Synthesis, Biological, Spectroscopic and Computational Investigations of Novel N-Acylhydrazone Derivatives of Pyrrolo[3,4-d]Pyridazinone as Dual COX\/LOX Inhibitors. Molecules, 28.","DOI":"10.3390\/molecules28145479"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6617","DOI":"10.1039\/D4RA00450G","article-title":"Stereochemical Insights into \u03b2-Amino-N-Acylhydrazones and Their Impact on DPP-4 Inhibition","volume":"14","author":"Reina","year":"2024","journal-title":"RSC Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111677","DOI":"10.1016\/j.cbi.2025.111677","article-title":"N-Acyl Hydrazone Derivatives Reduce pro-Inflammatory Cytokines, INOS and COX-2 in Acute Lung Inflammation Model","volume":"420","author":"Silva","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/cvr\/cvae047","article-title":"SGLT2 Inhibitors: From Glucose-Lowering to Cardiovascular Benefits","volume":"120","author":"Preda","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41594-023-01134-0","article-title":"Transport and Inhibition Mechanism of the Human SGLT2\u2013MAP17 Glucose Transporter","volume":"31","author":"Hiraizumi","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1038\/s41598-024-52331-w","article-title":"Effect of Pharmacological Selectivity of SGLT2 Inhibitors on Cardiovascular Outcomes in Patients with Type 2 Diabetes: A Meta-Analysis","volume":"14","author":"Sayour","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108209","DOI":"10.1016\/j.bioorg.2025.108209","article-title":"The Discovery of a New Uncompetitive Inhibitor of Nucleoside Hydrolase from Leishmania Donovani","volume":"156","author":"Alves","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1007\/s00125-018-4654-7","article-title":"Development of SGLT1 and SGLT2 Inhibitors","volume":"61","author":"Rieg","year":"2018","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1021\/ci034243x","article-title":"ESOL: Estimating Aqueous Solubility Directly from Molecular Structure","volume":"44","author":"Delaney","year":"2004","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mauri, A., and Bertola, M. (2022). Alvascience: A New Software Suite for the QSAR Workflow Applied to the Blood\u2013Brain Barrier Permeability. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112882"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1021\/jm0492002","article-title":"A Bioavailability Score","volume":"48","author":"Martin","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1021\/ci990307l","article-title":"Prediction of Physicochemical Parameters by Atomic Contributions","volume":"39","author":"Wildman","year":"1999","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/acsfoodscitech.5c00074","article-title":"Chemical Composition and Antidiabetic Potential of a Phenolic-Rich Extract from Cashew Fiber","volume":"5","author":"Filho","year":"2025","journal-title":"ACS Food Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0003-2697(62)90014-3","article-title":"A Method for the Colorimetric Estimation of Glycogen with Lodine","volume":"4","author":"Krisman","year":"1962","journal-title":"Anal. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of Total, Protein-Bound, and Nonprotein Sulfhydryl Groups in Tissue with Ellman\u2019s Reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0076-6879(90)86135-I","article-title":"Malondialdehyde Determination as Index of Lipid Peroxidation","volume":"186","author":"Draper","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Draper, H.H., and Hadley, M. (1988). Malondialdehyde Derivatives in Urine. Oxygen Radicals in Biology and Medicine, Springer.","DOI":"10.1007\/978-1-4684-5568-7_30"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0891-5849(93)90035-S","article-title":"A Comparative Evaluation of Thiobarbituric Acid Methods for the Determination of Malondialdehyde in Biological Materials","volume":"15","author":"Draper","year":"1993","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1152\/ajpregu.00187.2024","article-title":"Water Deprivation Induces a Systemic Procatabolic State That Differentially Affects Oxidative and Glycolytic Skeletal Muscles in Male Mice","volume":"328","author":"Costa","year":"2025","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.bbagen.2014.10.001","article-title":"The Mechanism of Action of Ursolic Acid as Insulin Secretagogue and Insulinomimetic Is Mediated by Cross-Talk between Calcium and Kinases to Regulate Glucose Balance","volume":"1850","author":"Castro","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1210\/jcem-68-2-374","article-title":"Estimates of In Vivo Insulin Action in Man: Comparison of Insulin Tolerance Tests with Euglycemic and Hyperglycemic Glucose Clamp Studies","volume":"68","author":"Bonora","year":"1989","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00330","DOI":"10.1016\/j.plabm.2023.e00330","article-title":"Performance Evaluation of QuantStudio 1 plus Real-Time PCR Instrument for Clinical Laboratory Analysis: A Proof-of-Concept Study","volume":"36","author":"Wang","year":"2023","journal-title":"Pract. Lab. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/829\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T06:16:46Z","timestamp":1768544206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020829"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020829","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}