Anti-tuberculosis effect and safety of diarylquinoline compounds

Abstract:

[Background] Bedaquiline is the special medicine for the treatment of tuberculosis. The diarylquinolines were kinds of compounds which were synthesized by the quinoline skeleton, and were rarely reported about its research on the anti-tuberculosis. [Objective] The bacteriostatic effect on Mycobacterium tuberculosis and drug safety of diarylquinoline compounds (H2) were studied, laying the foundation for drug research and development. [Methods] First, the minimum inhibitory concentration (MIC) and minnium bactericidal concentration (MBC) of H2 against different Mycobacterium tuberculosis were determined by proportional method, and the first-line anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol) were selected as positive control. The results were observed four weeks later. 40 kunming mice were divided into 5 dose groups. The survival status and appearance signs of Kunming mice at different doses were observed by gavage. According to the dose of LD50, three dose groups (high, mid, low) and blank control group were fed with 7 days. At the end of the experiment, the peripheral blood was examined, the organs were weighed, the tissue sections were made, and the pathological changes were observed. [Results] In vitro bacteriostatic test showed that the MIC of H2 to H37Rv is similar to INH, and it still has a good bacteriostatic effect on drug-resistant strains. In vivo toxicity test showed that the LD50 of mice was 582.77 mg/kg. Compared with the control group, in the high dose group, the body mass was very significantly different at the 5th day (P<0.01), and at the 6th and 7th day were significantly different (P<0.05), and the red blood cell, platelet, plateletocrit (P<0.05), and the liver coefficient (P<0.01). Microscopic results showed that there were mild inflammation and edema in renal tissue, and mild vesicular degeneration in renal tubular epithelial tissue, and mild edema in liver and necrosis of hepatocytes in the dose group. [Conclusion] The compound has good bacteriostatic effect on different Mycobacterium tuberculosis, bringing significance of further development and optimization.