ACTIVITY OF HYDRAZONE AND ACYLHYDRAZONES AGAINST MYCOBACTERIUM TUBERCULOSIS CLINICAL ISOLATES

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex, and with high mortality rates. The first-line treatment against the disease, using isoniazid, rifampicin, ethambutol and pyrazinamide, is well established, but nonetheless the treatment dropout rate is high. The emergence of drug resistant strains currently used has become a worldwide concern, especially with the advent of multidrug-resistant (MDR) and extensively resistant (XDR) tuberculosis. Because of this, it is essential the research for new compounds, which may be more effective and promising in the treatment of TB. Hydrazones and acylhydrazones are compounds widely studied because of their wide spectrum of activity. The objective of this work was to determine the minimum inhibitory concentration (MIC) of hydrazone and acylhydrazone derivatives against clinical isolates of Mtb. The MIC determination of one hydrazone and four acylhydrazones against five clinical isolates was determined by the resazurin microtiter assay plate (REMA) method. Hydrazone and acylhydrazones at different concentrations (250 - 0.49 μg/mL) were serially diluted into 96-well microplates containing 7H9 medium supplemented with OADC (oleic acid, bovine albumin dextrose and catalase). Then, standardized clinical isolates using McFarland's scale 1 diluted 1:20 were added to the microplate. After incubation for seven days at 37 C, 0.02 % resazurin was added to the wells, which was further incubated for 24 h. MIC was determined as the well where there was no visible change in the color of resazurin, indicating inhibition of mycobacterial growth. The clinical isolates used have different resistance profiles, one pan-susceptible and four MDR. The five derivatives tested were able to inhibit bacterial growth of the clinical isolates tested, with MICs less than or equal to 250 μg/mL. For isolate 49 (susceptible), the best MIC were observed, varying between 0.49 - 62.5 μg/mL, and the ACHCOI-17 derivative had MIC equivalent to 0.49 μg/mL, better than ethambutol, a first-line anti-TB drug. For isolates MDR 109, 73A, 64A and 3614, the MICs of the derivatives ranged from 3.9 to 62.5 μg/mL, 7.8 to 250 μg/mL, 7.8 to 125 μg/mL and 3.9 to 125 μg/mL, respectively. All derivatives have been effective in inhibiting the bacterial growth of clinical isolates, including MDR, and are therefore considered promising compounds for the treatment of TB. Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex, and with high mortality rates. The first-line treatment against the disease, using isoniazid, rifampicin, ethambutol and pyrazinamide, is well established, but nonetheless the treatment dropout rate is high. The emergence of drug resistant strains currently used has become a worldwide concern, especially with the advent of multidrug-resistant (MDR) and extensively resistant (XDR) tuberculosis. Because of this, it is essential the research for new compounds, which may be more effective and promising in the treatment of TB. Hydrazones and acylhydrazones are compounds widely studied because of their wide spectrum of activity. The objective of this work was to determine the minimum inhibitory concentration (MIC) of hydrazone and acylhydrazone derivatives against clinical isolates of Mtb. The MIC determination of one hydrazone and four acylhydrazones against five clinical isolates was determined by the resazurin microtiter assay plate (REMA) method. Hydrazone and acylhydrazones at different concentrations (250 - 0.49 μg/mL) were serially diluted into 96-well microplates containing 7H9 medium supplemented with OADC (oleic acid, bovine albumin dextrose and catalase). Then, standardized clinical isolates using McFarland's scale 1 diluted 1:20 were added to the microplate. After incubation for seven days at 37 C, 0.02 % resazurin was added to the wells, which was further incubated for 24 h. MIC was determined as the well where there was no visible change in the color of resazurin, indicating inhibition of mycobacterial growth. The clinical isolates used have different resistance profiles, one pan-susceptible and four MDR. The five derivatives tested were able to inhibit bacterial growth of the clinical isolates tested, with MICs less than or equal to 250 μg/mL. For isolate 49 (susceptible), the best MIC were observed, varying between 0.49 - 62.5 μg/mL, and the ACHCOI-17 derivative had MIC equivalent to 0.49 μg/mL, better than ethambutol, a first-line anti-TB drug. For isolates MDR 109, 73A, 64A and 3614, the MICs of the derivatives ranged from 3.9 to 62.5 μg/mL, 7.8 to 250 μg/mL, 7.8 to 125 μg/mL and 3.9 to 125 μg/mL, respectively. All derivatives have been effective in inhibiting the bacterial growth of clinical isolates, including MDR, and are therefore considered promising compounds for the treatment of TB Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex, and with high mortality rates. The first-line treatment against the disease, using isoniazid, rifampicin, ethambutol and pyrazinamide, is well established, but nonetheless the treatment dropout rate is high. The emergence of drug resistant strains currently used has become a worldwide concern, especially with the advent of multidrug-resistant (MDR) and extensively resistant (XDR) tuberculosis. Because of this, it is essential the research for new compounds, which may be more effective and promising in the treatment of TB. Hydrazones and acylhydrazones are compounds widely studied because of their wide spectrum of activity. The objective of this work was to determine the minimum inhibitory concentration (MIC) of hydrazone and acylhydrazone derivatives against clinical isolates of Mtb. The MIC determination of one hydrazone and four acylhydrazones against five clinical isolates was determined by the resazurin microtiter assay plate (REMA) method. Hydrazone and acylhydrazones at different concentrations (250 - 0.49 μg/mL) were serially diluted into 96-well microplates containing 7H9 medium supplemented with OADC (oleic acid, bovine albumin dextrose and catalase). Then, standardized clinical isolates using McFarland's scale 1 diluted 1:20 were added to the microplate. After incubation for seven days at 37 C, 0.02 % resazurin was added to the wells, which was further incubated for 24 h. MIC was determined as the well where there was no visible change in the color of resazurin, indicating inhibition of mycobacterial growth. The clinical isolates used have different resistance profiles, one pan-susceptible and four MDR. The five derivatives tested were able to inhibit bacterial growth of the clinical isolates tested, with MICs less than or equal to 250 μg/mL. For isolate 49 (susceptible), the best MIC were observed, varying between 0.49 - 62.5 μg/mL, and the ACHCOI-17 derivative had MIC equivalent to 0.49 μg/mL, better than ethambutol, a first-line anti-TB drug. For isolates MDR 109, 73A, 64A and 3614, the MICs of the derivatives ranged from 3.9 to 62.5 μg/mL, 7.8 to 250 μg/mL, 7.8 to 125 μg/mL and 3.9 to 125 μg/mL, respectively. All derivatives have been effective in inhibiting the bacterial growth of clinical isolates, including MDR, and are therefore considered promising compounds for the treatment of TB Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex, and with high mortality rates. The first-line treatment against the disease, using isoniazid, rifampicin, ethambutol and pyrazinamide, is well established, but nonetheless the treatment dropout rate is high. The emergence of drug resistant strains currently used has become a worldwide concern, especially with the advent of multidrug-resistant (MDR) and extensively resistant (XDR) tuberculosis. Because of this, it is essential the research for new compounds, which may be more effective and promising in the treatment of TB. Hydrazones and acylhydrazones are compounds widely studied because of their wide spectrum of activity. The objective of this work was to determine the minimum inhibitory concentration (MIC) of hydrazone and acylhydrazone derivatives against clinical isolates of Mtb. The MIC determination of one hydrazone and four acylhydrazones against five clinical isolates was determined by the resazurin microtiter assay plate (REMA) method. Hydrazone and acylhydrazones at different concentrations (250 - 0.49 μg/mL) were serially diluted into 96-well microplates containing 7H9 medium supplemented with OADC (oleic acid, bovine albumin dextrose and catalase). Then, standardized clinical isolates using McFarland's scale 1 diluted 1:20 were added to the microplate. After incubation for seven days at 37 C, 0.02 % resazurin was added to the wells, which was further incubated for 24 h. MIC was determined as the well where there was no visible change in the color of resazurin, indicating inhibition of mycobacterial growth. The clinical isolates used have different resistance profiles, one pan-susceptible and four MDR. The five derivatives tested were able to inhibit bacterial growth of the clinical isolates tested, with MICs less than or equal to 250 μg/mL. For isolate 49 (susceptible), the best MIC were observed, varying between 0.49 - 62.5 μg/mL, and the ACHCOI-17 derivative had MIC equivalent to 0.49 μg/mL, better than ethambutol, a first-line anti-TB drug. For isolates MDR 109, 73A, 64A and 3614, the MICs of the derivatives ranged from 3.9 to 62.5 μg/mL, 7.8 to 250 μg/mL, 7.8 to 125 μg/mL and 3.9 to 125 μg/mL, respectively. All derivatives have been effective in inhibiting the bacterial growth of clinical isolates, including MDR, and are therefore considered promising compounds for the treatment of TB Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex, and with high mortality rates. The first-line treatment against the disease, using isoniazid, rifampicin, ethambutol and pyrazinamide, is well established, but nonetheless the treatment dropout rate is high. The emergence of drug resistant strains currently used has become a worldwide concern, especially with the advent of multidrug-resistant (MDR) and extensively resistant (XDR) tuberculosis. Because of this, it is essential the research for new compounds, which may be more effective and promising in the treatment of TB. Hydrazones and acylhydrazones are compounds widely studied because of their wide spectrum of activity. The objective of this work was to determine the minimum inhibitory concentration (MIC) of hydrazone and acylhydrazone derivatives against clinical isolates of Mtb. The MIC determination of one hydrazone and four acylhydrazones against five clinical isolates was determined by the resazurin microtiter assay plate (REMA) method. Hydrazone and acylhydrazones at different concentrations (250 - 0.49 μg/mL) were serially diluted into 96-well microplates containing 7H9 medium supplemented with OADC (oleic acid, bovine albumin dextrose and catalase). Then, standardized clinical isolates using McFarland's scale 1 diluted 1:20 were added to the microplate. After incubation for seven days at 37 C, 0.02 % resazurin was added to the wells, which was further incubated for 24 h. MIC was determined as the well where there was no visible change in the color of resazurin, indicating inhibition of mycobacterial growth. The clinical isolates used have different resistance profiles, one pan-susceptible and four MDR. The five derivatives tested were able to inhibit bacterial growth of the clinical isolates tested, with MICs less than or equal to 250 μg/mL. For isolate 49 (susceptible), the best MIC were observed, varying between 0.49 - 62.5 μg/mL, and the ACHCOI-17 derivative had MIC equivalent to 0.49 μg/mL, better than ethambutol, a first-line anti-TB drug. For isolates MDR 109, 73A, 64A and 3614, the MICs of the derivatives ranged from 3.9 to 62.5 μg/mL, 7.8 to 250 μg/mL, 7.8 to 125 μg/mL and 3.9 to 125 μg/mL, respectively. All derivatives have been effective in inhibiting the bacterial growth of clinical isolates, including MDR, and are therefore considered promising compounds for the treatment of TB