Abstract

COMPARATIVE STUDY OF ANTIBACTERIAL ACTIVITY OF PYRAZINE–PIPERIDINE AMIDES AGAINST COMMON PATHOGENIC BACTERIA

Kiruthiga Prakash, Mohanraj Raja, Mounishwaran Kamalesan, Rameshkumar

Abstract

The rising incidence of antibiotic-resistant bacterial infections underscores the urgent need for the development of innovative antibacterial agents that can surpass existing therapeutic constraints. Heterocyclic frameworks, especially those that incorporate pyrazine and piperidine pharmacophores, have demonstrated exceptional potential due to their improved biological compatibility and extensive pharmacological effects. In this research, a newly synthesized pyrazine–piperidine amide derivative was tested for its antibacterial efficacy against clinically significant Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) pathogens using the agar well diffusion method. This compound showed significant antibacterial activity that increased in a concentration-dependent fashion at 25, 50, 75, and 100 μg/mL. The highest level of inhibition was observed for S. aureus (19.3 ± 0.5 mm) and B. subtilis (18.5 ±0.6 mm) at the maximum concentration, exceeding the inhibitory effect of the standard ciprofloxacin on S. aureus. The compound generated inhibition zones of 15.2 ± 0.3 mm (100 μg/mL) against E. coli, while K. pneumoniae exhibited a zone of inhibition of 13.8 ± 0.4 mm (100 μg/mL). In contrast, ciprofloxacin showed a ZOI of 14.3 ± 0.5 mm. Moderate yet encouraging inhibition was also noted against Gram-negative strains. The improved antimicrobial efficacy is attributed to synergistic structural attributes that facilitate better bacterial membrane penetration and enzyme interaction. Overall, the findings suggest that the synthesized pyrazine–piperidine amide derivative holds promise as an antibacterial lead compound, particularly against Gram-positive pathogens. Additional investigations involving MIC/MBC determination, analysis of mechanistic pathways, cytotoxicity assessment, and structural optimization are recommended to aid its advancement towards drug development.

Keywords: Pyrazine–Piperidine; Antibacterial activity; Staphylococcus aureus; Escherichia coli; Klebsiella pneumonia.