Antimycobacterial, Molecular Docking and ADME Studies of Spiro Naphthyridine Pyrimidine and N‐(Quinolin‐8‐yl)acetamide Derivatives

Abstract

Two series of compounds viz., spiro naphthyridine pyrimidine derivatives and N-(quinolin-8-yl)acetamide derivatives which possess the quinoline core moiety were designed and synthesized. The spectral analysis viz., FT-IR, 1 H-NMR, 13 C-NMR and mass was carried out to establish the structures for the synthesized compounds. In vitro anti-tubercular activity was done against Mycobacterium tuberculosis H37Rv by following "microplate alamar blue assay (MABA)". The synthesized compounds showed good anti-tuberculosis (TB) activity with the least minimum inhibitory concentration (MIC) value of 6.25 μg/ mL. Computational molecular docking studies were performed out with Mycobacterium tuberculosis enoyl reductase (INHA) (PDB code: 4TZK) using AutoDock to predict the key binding interactions responsible for the activity and the Swiss ADME (absorption, distribution, metabolism, and excretion) tool computed the in silico drug likeliness properties. The synthesized title compounds create a way for the optimization and development of potential drugs against tuberculosis.

Design, synthesis, and anti-mycobacterial evaluation of 1,8-naphthyridine-3-carbonitrile analogues

“…44,45 Literature reports indicate that the presumed mechanism of action of anti-mycobacterial naphthyridine compounds involves inhibiting InhA. 46 Hence, we selected the InhA enzyme, with PDB ID 4TZK, as the target for conducting docking studies of our compounds, which are based on the naphthyridine nucleus. We conducted molecular docking studies of the most active anti-TB compound ANA-12 against Mtb InhA (PDB ID 4TZK).…”