Synthesis, Antimicrobial Activity, Structure-Activity Relationship, and Molecular Docking Studies of Indole Diketopiperazine Alkaloids.

Strategies for the synthesis of indole diketopiperazine alkaloids (indole DKPs) have been described and involve three analogs of indole DKPs. The antimicrobial activity and structure-activity relationship (SAR) of 24 indole DKPs were explored. Compounds and were found to be the most active, with minimum inhibitory concentrations (MIC) values in the range of 0.94-3.87 μM (0.39-1.56 μg/mL) against the four tested bacteria (, and ). Furthermore, compounds and displayed broad-spectrum antimicrobial activity with MIC values of 1.10-36.9 μM (0.39-12.5 μg/mL) against all tested bacteria and plant pathogenic fungi ( and ). According to the study, compounds showed significant binding affinity to the FabH protein from , which has been identified as the key target enzyme of fatty acid synthesis (FAS) in bacteria. Therefore, these compounds are not only promising new antibacterial agents but also potential FabH inhibitors.