EVALUATION OF THE SELECTIVITY INDEX OF ACYLHYDRAZONES DERIVATIVES AS POTENTIAL CANDIDATES FOR ANTI-TUBERCULOSIS DRUGS

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (Mtb) complex and has high mortality rates. Treatment for the disease, which lasts for at least 6 months, although well established, generates many adverse effects and is highly toxic to the patient. Because of this, treatment abandonment rates are high, and therefore, the search for new compounds that are effective against the bacillus and, at the same time, less toxic to the patient is extremely important. Acylhydrazones are bases of schiff, which has been widely studied for having several activities, like antimalarial, antimicrobial and antiviral. Thus, the aim of this study was to determine the selectivity index (SI) of three acylhydrazones derivatives. For this, the minimum inhibitory concentration (MIC) of the compounds is determined using the resazurin microtiter assay plate (REMA) with Mtb H37Rv and different concentrations of the acylhydrazones (250 – 0.49 μg/mL). MIC was determined as the point at which there was no reduction of resazurin from blue to pink, indicating inhibition of bacterial growth. The cytotoxic concentration for 50 % cells (IC50) in Vero cells was evaluated by the MTT reduction method using 5.0 × 105 cells/ml, which were incubated with different concentrations of the derivatives (250 – 3.12 μg/mL). The MICs ranged between 0.97 and 31.25 μg/mL, being 0.97 μg/mL, 15.6 μg/mL and 31.25 μg/mL, for derivatives (1), (2) and (3), respectively. The IC50 of the three derivatives was 26.8 μg/mL for derivative (1), 27.0 μg/mL for (2), and 55.0 μg/mL to the acylhydrazones (3). The SI was calculated with the ratio of IC50/MIC of the acylhydrazones. The derivative (1) show the best IS (26.7), while the derivatives (2) and (3) obtained inferior results, of 1.7 and 1.8, respectively. Compounds with SI above 10, are considered great candidates for future drugs, since they present a much greater toxicity to the bacillus than to the patient. Thus, acylhydrazone (1) is a major anti-TB drug candidate. Acylhydrazones (2) and (3), although showing lower results, are also more harmful to bacteria than to mammalian cells. Further studies should be done to improve understanding of anti-TB action.