Novel quinoline–imidazole derivatives as inhibitors of Mycobacterium tuberculosis : an integrated approach combining molecular dynamics and in-vitro studies

The rationale for designing and synthesising quinoline–imidazole hybrids as antitubercular and cytotoxic agents stems from the strategic combination of two bioactive structural motifs to create compounds with enhanced efficacy, dual targeting, and potential to overcome drug resistance challenges in tuberculosis treatment. Herein, we report the design and synthesis of quinoline–imidazole hybrids. FTIR, Mass, 1H-NMR and 13C-NMR spectral data characterised the synthesised compounds. These compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv and cytotoxic activity against Hep G2, normal mouse fibroblast L929 cell lines. The antitubercular evaluation revealed that compound 6 g exhibited promising antitubercular activities with a MIC value of 6.26 µg/ml, while, compounds 6d, 6 h and 6i showed moderate MTB inhibition. Additionally, compound 6d demonstrated cytotoxicity against HepG2 cell lines with an IC50 value of 46.74 ± 1.209 μg/ml. Further selected compounds underwent theoretical investigation via molecular docking, stability assessment via MD trajectories and quantum computations to justify the experimental results. The obtained experimental and predicted in silico data indicate their potential to act as effective inhibitors.