Cytogenetic Activity of Newly Synthesized 1,5-Benzodiazepines in Normal Human Lymphocyte Cultures

Abstract

Many different types of benzodiazepine medications exist to treat a wide array of psychological and physical diseases based on dosage and implications. Benzodiazepines are generally considered as safe and effective drugs in short term; however, cognitive impairments and paradoxical effects occasionally occur. Our recent studies have shown that some 1,4-benzodiazepines exhibit cytogenetic activity (alprazolam, diazepam, and lorazepam) in normal human lymphocyte cultures. 1,5-Benzodiazepine derivatives are used in the synthesis of fused ring compounds, to study the chemical structure-pharmacological activity correlation. We synthesized four compounds of this category with small structural differences. The aim of this study was to investigate their cytogenetic activity in vitro at doses equivalent to the per os doses of the used 1,4-benzodiazepines. Sister chromatid exchanges (SCEs), proliferation rate index, and mitotic index were evaluated in lymphocytes of peripheral blood cultures from two healthy donors. Three of the newly synthesized compounds exhibited positive cytogenetic activity (statistically significant reduction of SCEs, p < 0.01, t-test), without showing cytostatic properties. The observed reduction of the lymphocytes' SCEs because of 1,5-benzodiazepines' activity is remarkable and requires further investigation to improve pharmacological effects.