lignans and Tuberculosis

Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to use more than one medication.. Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used.. Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies.. The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds, respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114 and 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters.. Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.

Topics: Antitubercular Agents; Bacterial Proteins; Humans; Lauraceae; Lignans; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Mycobacterium tuberculosis; Quantitative Structure-Activity Relationship; Tuberculosis

Tuberculosis remains a worldwide health problem and requires long-term treatment with several antibiotics; therefore, compliance problems and the emergence of multidrug resistance (MDR) are involved. (-)-Licarin A (LA) was isolated from diverse plants such as Aristolochia taliscana and possesses antimycobacterial, antiinflammatory, trypanocidal, and neuroprotective activities. The aim of the study was to determine the antitubercular and subacute toxicity of LA isolated from A. taliscana in BALB/c mice.. The antitubercular activity of LA was tested in a TB murine model inducing disease with M. tuberculosis H37Rv or MDR. Mice were treated with LA (5 mg/kg) for 30 and 60 days; post/treatment, lung bacilli loads and pneumonia percentage were determined. The subacute toxicity of LA (21 days) was evaluated in healthy mice. After treatment, biochemical and hematological parameters were determined and main organs were analyzed histologically.. In animals infected with drug-sensitive or MDR strains, LA produced a significant decrease of pulmonary bacillary burdens at day 30 of treatment, and a significant pneumonia reduction at days 30 and 60 of treatment. Regarding subacute toxicity, LA administration during 21 days showed no abnormalities in main-organ macro- and microarchitecture. Biochemical and hematological parameters analyzed showed no statistical differences between control and treated groups.. (-)-Licarin A reduces pneumonia of mice infected with both mycobacterium strains. Also, subacute toxicity of LA exhibits no major signs of damage. Biochemical and hematological parameters and histological analyses indicate that LA caused no significant changes at the doses assayed.

Topics: Animals; Antitubercular Agents; Aristolochia; Drug Resistance, Multiple, Bacterial; Lignans; Lung; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Tuberculosis