Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD₅₀) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg/kg), and G4: HO-AAVPA (708 mg/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD₅₀ value of HO-AAVPA was greater than 2000 mg/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control (p ≤ 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug.

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.