Therapeutic Potential of a Novel Nitroheterocyclic Derivative in Experimental Tuberculosis Models in C57BL/6 Mice Infected with Biologically Diverse Mycobacteria
Abstract
Introduction. Drug-resistant Mycobacterium tuberculosis remains a major challenge for tuberculosis treatment. This study evaluated the therapeutic efficacy of the novel nitroheterocyclic compound LK 1674 in murine models of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis. Materials and Methods. Male C57BL/6 mice were infected intravenously with either the DS strain H37Rv or the clinical MDR Beijing strain 5582. LK 1674 was administered orally as monotherapy (10 mg/kg) and compared with ethambutol (E), moxifloxacin (Mfx), and linezolid (Lzd). Treatment efficacy was assessed by microbiological, morphometric, and histopathological analyses. Results. In the DS model, LK 1674 significantly increased pulmonary bacterial clearance (2.1-fold; p < 0.02), reduced lung and spleen weights, decreased lung pathology scores, and attenuated inflammatory lesions. Enhanced local immune responses were associated with expansion of inducible bronchus-associated lymphoid tissue (iBALT). Its efficacy was comparable to Mfx but lower than E and Lzd. In the MDR model, LK 1674 significantly reduced pulmonary mycobacterial burden (p < 0.003) and lung pathology scores (p < 0.004) and promoted iBALT proliferation. Across most evaluated parameters, its activity was comparable to that of Mfx. Conclusion. LK 1674 exhibited antitubercular activity in both DS and MDR tuberculosis models and warrants further preclinical investigation as a potential anti-tuberculosis agent.
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