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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Type 2 diabetes (T2D) is a multifactorial metabolic disease in which hyperglycemia coexists with insulin resistance, \u03b2-cell dysfunction, dyslipidemia, and progressive microvascular and macrovascular complications. The structural versatility of the benzothiazole scaffold has enabled the development of a diverse array of preclinical compounds capable of modulating multiple diabetes-relevant targets. This review critically analyzes the available evidence on benzothiazole-derived compounds exhibiting antidiabetic or other diabetes-related pharmacological activities. No lower publication-date limit was imposed, and the literature included in the review ranged from 1997 to March 2026, encompassing in silico, in vitro, ex vivo, and in vivo evidence. The compounds are discussed according to their primary molecular targets, including \u03b1-glucosidase and \u03b1-amylase, dipeptidyl peptidase-4 (DPP-4), peroxisome proliferator-activated receptor -\u03b3 (PPAR-\u03b3), protein tyrosine phosphatase 1B (PTP1B), glycogen phosphorylase, 11\u03b2-hydroxysteroid dehydrogenase 1 (11\u03b2-HSD1), aldose reductase, AMPK, and other emerging metabolic targets. Structure\u2013activity relationships (SAR) are highlighted, demonstrating that C-2 functionalization, substitution at the C-5 and C-6 positions, halogenation, the presence of electron-donating or electron-withdrawing groups, and hybridization with thiazolidinedione, rhodanine, triazole, oxadiazole, and other pharmacophores can markedly alter potency, selectivity, and metabolic effects. Various derivatives have matched or outperformed reference agents such as acarbose, glibenclamide, pioglitazone, or aldose reductase inhibitors in preclinical assays. However, a direct comparison between studies is limited by the heterogeneity of models, endpoints, units, and dosing regimens, and clinical efficacy for T2D has not yet been established for this chemical class. Overall, the benzothiazole scaffold emerges not as a universal antidiabetic pharmacophore, but as a highly adaptable platform for the rational design of multitarget compounds.<\/jats:p>","DOI":"10.3390\/ijms27198863","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:31:31Z","timestamp":1791203491000},"page":"8863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Benzothiazole-Derived Compounds as Potential Drugs for the Treatment of Type 2 Diabetes: A Descriptive Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Ana Mar\u00eda","family":"Correa-Basurto","sequence":"first","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-303X","authenticated-orcid":false,"given":"Miguel","family":"Valdes","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades 2 Piso CORSE Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06725, Mexico"},{"name":"Laboratorio de Inmunolog\u00eda, Departamento de Sistemas Biol\u00f3gicos, Universidad Aut\u00f3noma Metropolitana Unidad Xochimilco, Calz. del Hueso 1100, Coapa, Villa Quietud, Coyoac\u00e1n, Ciudad de M\u00e9xico 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Cristina","family":"Cabrera-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnolog\u00eda, Instituto Polit\u00e9cnico Nacional, Av. Acueducto s\/n, Barrio La Laguna Ticom\u00e1n, Ciudad de M\u00e9xico 07340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9378-4063","authenticated-orcid":false,"given":"Natalia Reyes","family":"Vallejo","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6255-9112","authenticated-orcid":false,"given":"Alejandro","family":"Cruz","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnolog\u00eda, Instituto Polit\u00e9cnico Nacional, Av. Acueducto s\/n, Barrio La Laguna Ticom\u00e1n, Ciudad de M\u00e9xico 07340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0012-580X","authenticated-orcid":false,"given":"Martha Cecilia","family":"Rosales-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-957X","authenticated-orcid":false,"given":"Juan Andres","family":"Alvarado-Salazar","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"},{"name":"Licenciatura de Qu\u00edmica Farmac\u00e9utico Biol\u00f3gica, \u00c1rea Farmac\u00e9utica, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Batalla 5 de mayo s\/n, Ej\u00e9rcito de Oriente, Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"},{"name":"Academia de Farmacolog\u00eda y Toxicolog\u00eda, Licenciatura de Qu\u00edmica Farmac\u00e9utico Biol\u00f3gica, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Batalla 5 de mayo s\/n, Ej\u00e9rcito de Oriente, Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-9875","authenticated-orcid":false,"given":"Jessica Elena","family":"Mendieta-Wejebe","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ecl.2021.05.013","article-title":"An Update on the Epidemiology of Type 2 Diabetes: A Global Perspective","volume":"50","author":"Tinajero","year":"2021","journal-title":"Endocrinol. 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