Molecular Docking, Synthesis, Characterization of Novel Pyridine/ Piperidine N-Mannich Base Derivatives and their Bactericidal Studies

Abstract

OBJECTIVE This study aims to synthesize and estimate the anti-bacterial, anti-fungal and anti-tubercular activity of novel N-pyridine/piperidine Mannich base derivatives (M1-M6).
METHODS The novel N-pyridine/piperidine Mannich base derivatives were prepared through condensation reactions between pyridine/piperidine, furfuraldehyde and various aromatic/ aliphatic amines. The structures of the synthesised compounds were characterized using FTIR,
¹³C-NMR, ¹H-NMR, and mass spectroscopy. These derivatives were assessed for anti- bacterial, anti-fungal and anti-tubercular activity using in vitro methods such as paper disc diffusion and agar well diffusion methods.
RESULTS The antimicrobial and antitubercular activities of the Schiff base Mannich derivatives (M1–M6) were systematically evaluated. Antimicrobial screening against bacterial strains (S. aureus, E. coli, S. epidermidis, and P. aeruginosa) and fungal strains (Aspergillus fumigatus and A. niger) demonstrated clear concentration-dependent activity. At a concentration of 100 μg/disc, compound M2 exhibited notable inhibition zones of 10.25 mm (S. aureus), 9.76 mm (E. coli), and 10.43 mm (A. fumigatus), while M4 showed comparable activity with 10.03 mm, 8.56 mm, and 9.87 mm, respectively. In contrast, M3 displayed the lowest activity, especially against P. aeruginosa and fungal strains, whereas M5 and M6 showed moderate effects. Standard drugs, ciprofloxacin and fluconazole, exhibited superior
potency. In antitubercular assays, M2 and M4 showed dose-dependent inhibition of mycobacterium, with M2 demonstrating higher efficacy. Docking
studies further supported these findings, as M2 and M4 showed strong binding affinities toward InhA and EthR proteins, correlating well with their biological activity.
CONCLUSION These findings emphasize the therapeutic promise of Mannich base derivatives, particularly piperidine-containing compounds (M2, M4), as potential antimicrobial and antitubercular agents. Their higher basicity enhances molecular interactions with microbial targets. Further structural optimization of these scaffolds could improve potency, selectivity, and effectiveness against resistant bacteria, fungi, and Mycobacterium tuberculosis.