New pharmaceutical materials with analgesic activity based on 1,2,3-triazolo-1,4-benzodiazepine

Abstract

Medicines and their components are essential molecular functional materials while developing and transferring them into production is a priority for many interdisciplinary research teams. Hybrid compounds that integrate multiple potent pharmacophoric fragments are regarded as highly promising candidates in the development of such materials. Hence, the incorporation of 1,2,3-triazole moieties into conventional 1,4-benzodiazepine frameworks presents a promising strategy. This structural modification is anticipated to enhance drug-receptor interactions and improve pharmacological profiles by increasing selectivity for specific GABA-A receptor subtypes. The objective of this study was to assess new functional materials for pharmaceutical use derived from 1,2,3-triazolo-1,4-benzodiazepine compounds. The research specifically focused on conducting molecular docking studies at the benzodiazepine site of the GABA receptor, evaluating their safety profile in vitro, and determining their analgesic potential in vivo. During the molecular docking study of five compounds for their binding affinity towards the benzodiazepine site of the GABA receptor, a detailed analysis of the formed complexes indicated that all S-configurations of the new compounds exhibit a binding mode in the benzodiazepine site comparable to classical benzodiazepines. The findings demonstrated that the investigated derivatives do not negatively impact cell proliferation in the MTT and NRU tests. No genotoxicity of the investigated derivatives was observed under the conditions of the umu-test. Additionally, it has been established that the compounds exhibit moderate antinociceptive activity in experimental models involving both peripheral and central mechanisms of pain reaction formation.