Synthesis, Molecular Docking Studies and In Vitro Antimicrobial Evaluation of Peptide Linked Trifluoromethyl Triazolo‐Pyrazine Derivatives

ABSTRACT The rapid increase in multidrug‐resistant microbial pathogens has emerged as a major global challenge, making it essential to develop and discover new, highly potent, broad‐spectrum therapeutic agents. The heterocyclic framework has drawn considerable interest due to its wide range of biological activities, and the incorporation of a peptide can further enhance the selectivity. Herein, we report the synthesis of peptide‐linked trifluoromethyl triazolo‐pyrazine derivatives ( 7a‐e and 10a‐e ), characterized using 1 H NMR, 13 C NMR, mass spectrometry, and IR spectroscopy. All the synthesized compounds' antibacterial and antifungal activities were evaluated using a minimum inhibitory concentration (MIC) assay. Biological efficacy results revealed that compounds 7a and 7b displayed MIC values (20–35 μg/mL) that are comparable to or better than chloramphenicol (16–26 μg/mL). Likewise, antifungal assays revealed that compound 10d exhibited activity (67–82 μg/mL) notably superior to griseofulvin (130–160 μg/mL). The obtained data clearly indicate that the synthesized compounds are potent against microbes with the inclusion of structural diversity of peptide–triazolopyrazine conjugates. Furthermore, molecular docking studies show strong binding interactions of the potent compounds with their targets, as evidenced by docking scores comparable to or surpassing the control compounds. These findings provide a promising foundation for the development of next‐generation antimicrobial agents.