In vivo Acute Oral Toxicity Assessment of Novel Histone Deacetylase 2 Inhibitor

Histone deacetylases (HDACs) are enzymes responsible for removing acetyl groups from histone proteins, resulting in chromatin condensation and repression of genes. They regulate expression of genes, cell cycle, and multiple cellular processes. Hydroxamic acid is a well recognized moiety characterized by its potent zinc-binding capability, making it an effective inhibitor of HDACs. A novel hydroxamic acid based molecule, N ¹ -(2,2'-bipyridin-6-yl)-N ⁸ -hydroxyoctanediamide (compound 3B) was previously synthesized and the anticancer properties of the compound were examined in vitro in our laboratory. No prior toxicological study has been done on this compound. Therefore, the current investigation concentrated on the acute oral toxicity of compound 3B on female BALB/c mice, adhering to OECD 423 guidelines. In this study, compound 3B was given orally at 300 mg/kg body weight (b.w.) and 2000 mg/kg b.w. The food consumption and body weight of the mice did not differ significantly among the control and treated groups. Variations were observed in the levels of a few of the biochemical markers. Histopathological examination showed inflammatory infiltrate, and lesions in a few vital organs. The comprehensive investigation showed that compound 3B exhibited moderate toxic effects at a higher dosage of 2000 mg/kg in few organs and caused alterations in biochemical markers; however, it did not result in any mortality, indicating an LD ₅₀ value exceeding 2000 mg/kg. The dosage of compound 3B can be administered at levels below 2000 mg/kg for subsequent studies.