Synthesis of Hydroxybenzodiazepines with Potential Antioxidant and Antifungal Action

Abstract

Benzodiazepines derivatives are nitrogen heterocyclic compounds that have various industrial, synthetic, and medicinal applications. Therefore, its potential fully justifies every effort towards the improvement of new, selective, and competent production of these heterocyclic compounds. The novelty of this study encompasses the synthesis of new hydroxylated analogs of 1,5-benzodiazepine together with the evaluation of their biological potential as antioxidants and antifungals candidates. Additionally, the reported antifungal activity against fungi of the Sporothrix schenckii complex inaugurates an unprecedented property for this class of compounds. The results of biological activities assays suggest that the novel 2,7-dimethyl-2,4-bis(4-hydroxyphenyl)-2,3-dihydro1H-1,5-benzodiazepine possesses a high antifungal activity against all fungal strains evaluated of the Sporothrix genus and outstanding total antioxidant capacity. Besides, in silico studies have evidenced that the hydroxylated derivatives have the best aqueous solubility and cell permeability profile, which makes them superior in comparison with the commercial antifungal itraconazole, a drug commonly used in the treatment of sporotrichosis.