2‐DPC Mediated Effective Synthesis of Peptide Conjugates, their Antifungal and Antibacterial Properties

Abstract

The present work demonstrates the effective synthesis of amide derivatives of Nα‐protected amino acids and aryl/heteroaryl amines using di‐2‐pyridyl carbonate (2‐DPC) and cat. DMAP mediated coupling reaction. Several coupling methods were employed for the screening of the amides using EDC, HATU, mixed anhydride, T3P, CDI, COMU, DPTC, and 2‐DPC, where 2‐DPC/cat. DMAP method furnished amides with better yields and purity in shorter durations. Seventeen amide derivatives (3 a–3 q) were successfully synthesized using the present protocol and were characterized by NMR, mass and IR spectroscopy. Further, we performed the in‐silico and in‐vitro studies on the synthesized molecules on antifungal and antibacterial activity. Molecular docking studies reveal the binding affinity of protein‐ligand interactions ranging from −6.2 to −11.0 kcal/mol (Aspergillus Niger Esta), −5.9 to −9.9 kcal/mol (DNA gyrase subunit B) and −6.4 to −13.4 kcal/mol (CYP51B). Compounds like 3 d, 3 e, 3 h, 3 i, 3 j and 3 l exhibit the highest antibacterial and antifungal activity when compared to the standards delafloxacin, ketoconazole, and bifonazole in in‐silico studies. Whereas the in‐vitro studies also unveiled good antimicrobial activity with peptide conjugates. The results of antimicrobial activity exhibits in antifungal species show the good activity concentrations in compounds 3 j is 11.2±3.54 μg/mL and 3 l is 10.3±2.76 μg/mL. The anti‐bacterial species exhibit the compound 3 g showing good activity in different concentrations 12±3.08 μg/mL, 12.2±3.04 μg/mL, 12.6±2.78 μg/mL and 12.5±2.98 μg/mL.