A novel series of dipeptide derivatives containing indole-3-carboxylic acid conjugates as potential antimicrobial agents: the design, solid phase peptide synthesis, in vitro biological evaluation, and molecular docking study.

A new library of peptide-heterocycle hybrids consisting of an indole-3-carboxylic acid constituent conjugated with short dipeptide motifs was designed and synthesized by using the solid phase peptide synthesis methodology. All the synthesized compounds were characterized by spectroscopic techniques. Additionally, the synthesized compounds were subjected to in vitro antimicrobial activities. Two Gram-negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ) and two Gram-positive ( Streptococcus pyogenes and Staphylococcus aureus ) were used for the evaluation of the antibacterial activity of the targeted dipeptide derivatives. Good antibacterial activity was observed for the screened analogues by comparing their activities with that of ciprofloxacin, the standard drug. Also, two fungi ( Aspergillus niger and Candida albicans ) were employed for the evaluation of the antifungal activity of the synthesized compounds. When compared to the standard drug Fluconazole, it was observed that the screened analogues exhibited good antifungal activity. In continuation, all the synthesized derivatives were subjected to integrated molecular docking studies and molecular dynamics simulations to investigate binding affinities, intermolecular interaction networks, and conformational flexibilities with deoxyribonucleic acid (DNA) gyrase and lanosterol-14-alpha demethylase. The molecular docking studies revealed that indole-3-carboxylic acid conjugates exhibited encouraging binding interaction networks and binding affinity with DNA gyrase and lanosterol-14 alpha demethylase to show antibacterial and antifungal activity, respectively. Such synthesis, biological activity, molecular dynamics simulations, and molecular docking studies of short peptides with an indole conjugate unlock the door for the near future advancement of novel medicines containing peptide-heterocycle hybrids with the ability to be effective as antimicrobial agents.