One-Pot Synthesis of Novel β-Carboline-{α-Acylaminoamide}-Bisindole Derivatives: Antibacterial Evaluation, Molecular Docking, and Density Functional Theory Studies.

Abstract

A new series of β-carboline-{α-acylaminoamide}-bisindole hybrids (12a-l) is designed and synthesized employing an atom-economical one-pot Ugi four-component reaction (U-4CR), affording the target compounds in good yields. All synthesized compounds (12a-l) are characterized by NMR, infrared, and mass spectrometry and evaluated for their antibacterial activity against both Gram-positive and Gram-negative strains. Notably, compounds 12b, 12g, and 12h display comparable minimum inhibitory concentrations values (302-303 µg mL^-1) against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, showing markedly improved activity relative to their parent compounds 6 and 9, which show weaker inhibition (MIC = 308-623 µg mL^-1). Molecular docking studies of compounds 12g and 12h revealed favorable binding interactions with DNA gyrase, while density functional theory analysis supported their electronic reactivity. These findings highlight the potential of molecular hybridization in the development of novel antibacterial agents.