Structural modifications into diphenyl diselenide molecule do not cause toxicity in mice

Area of Science:

• Toxicology
• Medicinal Chemistry
• Pharmacology

Background:

• Diphenyl diselenide derivatives are explored for therapeutic potential.
• Understanding the toxicological profile of novel compounds is crucial for drug development.

Purpose of the Study:

• To evaluate the toxicological parameters of three diphenyl diselenide compounds: 1a (4,4'-dichloro-diphenyl diselenide), 1b (3,3'-ditrifluoromethyl-diphenyl diselenide), and 1c (4,4'-dimethoxyl-diphenyl diselenide).
• To assess the impact of structural modifications on compound toxicity in mice.

Main Methods:

• Oral administration of single doses of compounds 1a, 1b, and 1c to mice.
• Estimation of lethal dose 50 (LD50) values.
• Monitoring of body weight, food and water intake.
• Assay of δ-Aminolevulinate dehydratase (δ-ALA-D) and catalase activities.
• Evaluation of lipid peroxidation, vitamin C levels, and cerebral Na(+)/K(+)-ATPase activity.

Main Results:

• Estimated LD50 values were >381 mg/kg for 1a, 278 mg/kg for 1b, and >372 mg/kg for 1c.
• Compounds 1a and 1b significantly reduced body weight gain, food, and water intake.
• Inhibition of δ-ALA-D and catalase activities was observed with the highest doses of compounds 1a and 1b.
• No significant changes were noted in lipid peroxidation, vitamin C levels, or cerebral Na(+)/K(+)-ATPase activity.

Conclusions:

• The tested diphenyl diselenide compounds exhibit varying degrees of toxicity in mice.
• Compounds 1a and 1b demonstrate dose-dependent adverse effects, including reduced intake and inhibition of specific enzymes.
• Structural modifications in these diphenyl diselenide compounds did not lead to substantial increases in toxicity, supporting their further investigation in medicinal chemistry.