Salicil-hidrazonas: estudo insilico, síntese e avaliação de atividade antituberculose

Abstract

Tuberculosis is an ancient infectious disease caused by the bacillus Mycobacterium tuberculosis, which still has a high rate of contamination and deaths, especially in the last decade. The treatment is multichemotherapeutic, involving substances that are highly toxic, especially due to the time of exposure to some of them, since the treatment is long. In view of these diversities, a large number of individuals abandon the treatment aimed at eliminating the bacillus, and the emergence of strains that are multiresistant to the antibiotics used in therapy is common, exposing the need to seek new compounds with antituberculosis potential and with less toxicity during the period which treatment takes place. Salicylhydrazones are bioactive molecules frequently reported as substances with antibacterial and antiinflammatory action in the literature,motivating studies of compounds derived from these molecules. Thus, the present work presents the synthesis of two salicylhydrazones (2Furaldehyde salicylhydrazone(SH10) and 2Tiophenecarboxaldehyde salicylhydrazone (SH11)), from salicylic acid, with a view to evaluating the antiMycobacterium tuberculosis activity and carrying out in silico physicochemical parameters prediction studies. The compounds were obtained in yields ranging from 34.34% to 57.06%. The characterization of the compounds was performed using 1H and 13C nuclear magnetic resonance spectroscopy and infrared spectroscopy. The investigation of the in silico parameters was carried out for a series of 17 salicylhydrazones (SH1SH17) using the OSIRIS Property Explorer®, SwissADME®, PASS Online® and Molinspiration® software, provided data on the physicochemical properties about the capacity for oral bioavailability, toxicological action, predictions of pharmacological activities and bioactivity. The evaluation of the antituberculosis activity of salicylhidrazones SH1SH17 was carried out with the standard H37Rv strain and strains resistant to the drugs used in tuberculosis chemotherapy, aiming at identifying potential new drugs that can satisfactorily act as antituberculosis agents. The most active salicylhydrazones against the standard H37Rv strain of M. tuberculosis: MIC of 3.8 μg.mL1 (SH11), 7.9 μg.mL1 (SH10), 15.6 μg.mL1 (SH13 and SH14) and 31.25 μg.mL1 (SH8, SH12, SH15 and SH16). Finally, although the mechanism of action or the molecular targets for the proposed molecules is not known, it was observed that when inserted heterocyclic substituents it results in an improvement of the activity.