Preclinical Evaluation of 2-Aminobenzothiazole Derivatives: In Silico, In Vitro, and Preliminary In Vivo Studies as Diabetic Treatments and Their Complications

I tiakina i:
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I whakaputaina i:Molecules vol. 30, no. 16 (2025), p. 3427-3456
Kaituhi matua: Reyes-Vallejo, Natalia
Ētahi atu kaituhi: Valdes, Miguel, Reyes-Ramírez Adelfo, Alvarado-Salazar, Juan Andres, Cruz, Alejandro, Andrade-Jorge, Erik, Mendieta-Wejebe, Jessica Elena
I whakaputaina:
MDPI AG
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Urunga tuihono:Citation/Abstract
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022 |a 1420-3049 
024 7 |a 10.3390/molecules30163427  |2 doi 
035 |a 3244048427 
045 2 |b d20250101  |b d20251231 
084 |a 231541  |2 nlm 
100 1 |a Reyes-Vallejo, Natalia  |u Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politcnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico; reyes.natalia4@gmail.com (N.R.-V.); andres.alvarado.salazar@comunidad.unam.mx (J.A.A.-S.) 
245 1 |a Preclinical Evaluation of 2-Aminobenzothiazole Derivatives: In Silico, In Vitro, and Preliminary In Vivo Studies as Diabetic Treatments and Their Complications 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a 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–d, 8a–d, 11a–d, and 12c–d), starting with the in silico prediction of their properties, along with molecular docking against aldose reductase (ALR2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). All compounds complied with the main rules of pharmacological similarity and optimal affinity, highlighting 8d (ΔG = −8.39 kcal/mol for ALR2 and −7.77 kcal/mol for PPAR-γ). Selected compounds from families C and D were synthesized in moderate yields (~60%) and showed low acute oral toxicity (LD50 > 1250 mg/Kg). Compounds 8c and 8d inhibited ALR2 at concentrations below 10 µM. 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. 
653 |a Antidiabetics 
653 |a Physicochemical properties 
653 |a Pharmacokinetics 
653 |a Diabetes 
653 |a Molecular weight 
653 |a Metabolism 
653 |a Toxicity 
653 |a Hydrogen bonds 
653 |a Diabetic neuropathy 
653 |a Enzymes 
653 |a Permeability 
653 |a Bioavailability 
653 |a Oxidative stress 
700 1 |a Valdes, Miguel  |u Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politcnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico; reyes.natalia4@gmail.com (N.R.-V.); andres.alvarado.salazar@comunidad.unam.mx (J.A.A.-S.) 
700 1 |a Reyes-Ramírez Adelfo  |u Laboratorio de Síntesis Farmacéutica, Unidad Multidisciplinaria de Investigación Experimental Zaragoza, FES Zaragoza-Universidad Nacional Autonoma de México, Campus II. Batalla 5 de Mayo s/n, Ejército de Oriente Zona Peñón, Iztapalapa, Mexico City 09230, Mexico; adelfo.reyes@zaragoza.unam.mx 
700 1 |a Alvarado-Salazar, Juan Andres  |u Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politcnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico; reyes.natalia4@gmail.com (N.R.-V.); andres.alvarado.salazar@comunidad.unam.mx (J.A.A.-S.) 
700 1 |a Cruz, Alejandro  |u Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología, Departamento de Ciencias Básicas, Instituto Politécnico Nacional, Av. Acueducto s/n, Colonia Barrio La Laguna Ticomán, Mexico City 07340, Mexico; alcralmx@hotmail.com 
700 1 |a Andrade-Jorge, Erik  |u Laboratorio de Investigación en Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico; andrade136@hotmail.com 
700 1 |a Mendieta-Wejebe, Jessica Elena  |u Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politcnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico; reyes.natalia4@gmail.com (N.R.-V.); andres.alvarado.salazar@comunidad.unam.mx (J.A.A.-S.) 
773 0 |t Molecules  |g vol. 30, no. 16 (2025), p. 3427-3456 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3244048427/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/3244048427/fulltextwithgraphics/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3244048427/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch