{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:22Z","timestamp":1791244282192,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado of Instituto Polit\u00e9cnico Nacional","award":["SIPMULTI20242297"],"award-info":[{"award-number":["SIPMULTI20242297"]}]},{"name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado of Instituto Polit\u00e9cnico Nacional","award":["SIP20240101"],"award-info":[{"award-number":["SIP20240101"]}]},{"name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado of Instituto Polit\u00e9cnico Nacional","award":["SIP20250177"],"award-info":[{"award-number":["SIP20250177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Type 2 diabetes is a multifactorial disease characterized by chronic hyperglycemia, insulin resistance, oxidative stress, inflammation, and dyslipidemia, factors that contribute to the development of long-term complications. In this context, the 2-aminobenzothiazole scaffold has emerged as a promising candidate due to its broad spectrum of biological properties. In this study, we performed a multidisciplinary evaluation of benzothiazole derivatives (5a\u2013d, 8a\u2013d, 11a\u2013d, and 12c\u2013d), starting with the in silico prediction of their properties, along with molecular docking against aldose reductase (ALR2) and peroxisome proliferator-activated receptor gamma (PPAR-\u03b3). All compounds complied with the main rules of pharmacological similarity and optimal affinity, highlighting 8d (\u0394G = \u22128.39 kcal\/mol for ALR2 and \u22127.77 kcal\/mol for PPAR-\u03b3). Selected compounds from families C and D were synthesized in moderate yields (~60%) and showed low acute oral toxicity (LD50 &gt; 1250 mg\/Kg). Compounds 8c and 8d inhibited ALR2 at concentrations below 10 \u00b5M. In vivo studies using a streptozotocin-induced diabetic rat model with a high-fat diet revealed that compound 8d produced sustained antihyperglycemic effects and reduced insulin resistance, dyslipidemia, and polydipsia, without inducing hepatotoxicity or displaying intrinsic antioxidant or anti-inflammatory activity. These findings suggest that 8d is a promising candidate for further development in diabetes-related therapeutic strategies.<\/jats:p>","DOI":"10.3390\/molecules30163427","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"3427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preclinical Evaluation of 2-Aminobenzothiazole Derivatives: In Silico, In Vitro, and Preliminary In Vivo Studies as Diabetic Treatments and Their Complications"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9378-4063","authenticated-orcid":false,"given":"Natalia","family":"Reyes-Vallejo","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 Politcnico 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 Politcnico 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\u00e9mic 330, Col. Doctores, Mexico City 06720, 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, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-6075","authenticated-orcid":false,"given":"Adelfo","family":"Reyes-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de S\u00edntesis Farmac\u00e9utica, Unidad Multidisciplinaria de Investigaci\u00f3n Experimental Zaragoza, FES Zaragoza-Universidad Nacional Autonoma de M\u00e9xico, Campus II. Batalla 5 de Mayo s\/n, Ej\u00e9rcito de Oriente Zona Pe\u00f1\u00f3n, Iztapalapa, Mexico City 09230, 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 Politcnico 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, Departamento de Ciencias B\u00e1sicas, Instituto Polit\u00e9cnico Nacional, Av. 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