Assessment of the Anti-Tubercular Efficacy of a Hybrid Compound Using in vitro and in silico Methods

Background Tuberculosis is mostly caused by Mycobacterium tuberculosis; however, it can be caused by a variety of mycobacteria. Tuberculosis predominantly impacts the respiratory system, although it may also affect other areas of the body. Approximately 10% of latent infections advance to active disease and if left untreated, this condition has a death risk surpassing 50%. In recent years, numerous research investigations have been conducted to identify and produce anti-tuberculosis medications. Nevertheless, several of these treatments have exhibited undesirable effects and have evolved resistance to multiple therapies. Consequently, there remains a necessity for the advancement of a novel class of anti-tuberculosis pharmaceuticals.Materials and Methods We selected a new ligand for the in vitro and in silico evaluation of the antitubercular activity of 4-(3-(((1-phenyl-1H-1,2,3-triazol-4-yl) methoxy) methyl) quinolin-2-yl) morpholine using the MABA assay and AutoDock, respectively. This compound demonstrates elevated binding energies for the target proteins 4BAE (Bacterial DNA gyrase) and 2CIG (Bacterial DHFR).Results The MABA assay demonstrated that this compound at 200 µg and 100 µg exhibited inhibitory effects against M. smegmatis. The compound exhibits no anti-tubercular activity against Mtb (H37Ra), as the colour transition from blue to pink signifies the proliferation of mycobacteria. According to in silico studies, this compound functions by inhibiting bacterial DNA gyrase and topoisomerase IV. This may impede DNA synthesis and ultimately lead to bacterial mortality.Conclusion The selected compound exhibited anti-tubercular activity against the Mycobacterium smegmatis strain relative to the conventional rifampicin, but failed to show anti-tubercular activity against the H37ra.