# In vivo acute oral toxicity assessment of novel histone deacetylase 2 inhibitor

## TL;DR

This study evaluates the toxicity of a new HDAC inhibitor in mice and finds it has low toxicity at high doses.

## Contribution

The paper reports the first in vivo acute oral toxicity assessment of a novel hydroxamic acid-based HDAC2 inhibitor.

## Key findings

- Compound 3B showed moderate toxicity at 2000 mg/kg but no mortality.
- Biochemical markers and histopathology revealed minor organ effects at high doses.
- Compound 3B is classified as lowest toxicity (category 5) per OECD guidelines.

## Abstract

Histone deacetylases (HDACs) are enzymes responsible for removing acetyl groups from histone proteins, resulting in chromatin condensation and the repression of genes. They regulate the expression of genes, the cell cycle, and multiple cellular processes. Hydroxamic acid is a well-recognized moiety characterized by its potent zinc-binding ability, making it an effective inhibitor of HDACs. A novel hydroxamic acid-based molecule, N1-(2,2’-bipyridin-6-yl)-N8-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 performed on this compound. Therefore, the current investigation focused on the acute oral toxicity of compound 3B in 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.) or 2000 mg/kg b.w. The food consumption and body weight of the mice did not differ significantly between the control and treated groups. Variations were observed in the levels of a few of the biochemical markers. Histopathological examination revealed inflammatory infiltration and lesions in a few vital organs. The comprehensive investigation revealed that compound 3B exhibited moderate toxic effects at a relatively high dosage of 2000 mg/kg in few organs and caused alterations in biochemical markers; however, it did not result in any mortality, indicating that the LD50 value exceeded 2000 mg/kg. Compound 3B can be administered at concentrations less than 2000 mg/kg for subsequent studies.

The toxicity profile of compound 3B was studied in female BALB/c mice as per the OECD 423 guidelines.

Compound 3B was given through oral gavage at dosages of 300 mg/kg and 2000 mg/kg

Biochemical marker levels and histopathological examination revealed moderate toxic effects of compound 3B at 2000 mg/kg

Compound 3B is classified under category 5 (lowest toxicity) according to the OECD 423 guidelines.