Benzothiazole-Derived Compounds as Potential Drugs for the Treatment of Type 2 Diabetes: A Descriptive Review
6 affiliations
- 1Laboratorio de Biofísica y Biocatálisis, 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
- 2Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades 2 Piso CORSE Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Ciudad de México 06725, Mexico
- 3Laboratorio de Inmunología, Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Calz. del Hueso 1100, Coapa, Villa Quietud, Coyoacán, Ciudad de México 04960, Mexico
- 4Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Av. Acueducto s/n, Barrio La Laguna Ticomán, Ciudad de México 07340, Mexico
- 5Licenciatura de Química Farmacéutico Biológica, Área Farmacéutica, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Batalla 5 de mayo s/n, Ejército de Oriente, Iztapalapa, Ciudad de México 09230, Mexico
- 6Academia de Farmacología y Toxicología, Licenciatura de Química Farmacéutico Biológica, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Batalla 5 de mayo s/n, Ejército de Oriente, Iztapalapa, Ciudad de México 09230, Mexico
Abstract
Type 2 diabetes (T2D) is a multifactorial metabolic disease in which hyperglycemia coexists with insulin resistance, β-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 α-glucosidase and α-amylase, dipeptidyl peptidase-4 (DPP-4), peroxisome proliferator-activated receptor -γ (PPAR-γ), protein tyrosine phosphatase 1B (PTP1B), glycogen phosphorylase, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), aldose reductase, AMPK, and other emerging metabolic targets. Structure–activity 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.
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BibTeX
@article{correabasurto2026benzothiazolederived,
title = {{Benzothiazole-Derived Compounds as Potential Drugs for the Treatment of Type 2 Diabetes: A Descriptive Review}},
author = {Ana María Correa-Basurto and Miguel Valdes and Laura Cristina Cabrera-Pérez and Natalia Reyes Vallejo and Alejandro Cruz and Martha Cecilia Rosales-Hernández and Juan Andres Alvarado-Salazar and Jessica Elena Mendieta-Wejebe},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198863},
url = {https://www.mdpi.com/1422-0067/27/19/8863},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Benzothiazole-Derived Compounds as Potential Drugs for the Treatment of Type 2 Diabetes: A Descriptive Review
AU - Ana María Correa-Basurto
AU - Miguel Valdes
AU - Laura Cristina Cabrera-Pérez
AU - Natalia Reyes Vallejo
AU - Alejandro Cruz
AU - Martha Cecilia Rosales-Hernández
AU - Juan Andres Alvarado-Salazar
AU - Jessica Elena Mendieta-Wejebe
PY - 2026
DA - 2026/10/05
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198863
UR - https://www.mdpi.com/1422-0067/27/19/8863
AB - Type 2 diabetes (T2D) is a multifactorial metabolic disease in which hyperglycemia coexists with insulin resistance, β-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 α-glucosidase and α-amylase, dipeptidyl peptidase-4 (DPP-4), peroxisome proliferator-activated receptor -γ (PPAR-γ), protein tyrosine phosphatase 1B (PTP1B), glycogen phosphorylase, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), aldose reductase, AMPK, and other emerging metabolic targets. Structure–activity 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.
SN - 1422-0067
ER -