Microwave-assisted Synthesis and In Vitro and In Silico Studies of Novel Indole Derivatives as Antibacterial and Antifungal Agents

Background: Indole, a bicyclic heterocyclic compound consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring, is a versatile structural motif in medicinal chemistry. Its unique structure allows it to interact with various biological targets, making it a valuable scaffold in drug design. Indole derivatives have been widely explored for their pharmacological activities, including antibacterial, antipsychotic, anticholinergic, antiinflammatory, anticancer, antiviral, and antifungal properties. Their significant role in drug development underscores the need for continued research to discover and optimize novel indole-based compounds for improved therapeutic applications. Methods: A series of new 3-(2-(1H-indol-2-yl)phenyl)-2-(substituted phenyl)-3,4-dihydroimidazo [4,5-b]indoles (4a-4j) were synthesized by reacting 2-(o-aminophenyl)indole with aromatic aldehyde in the presence of ethanol. The structures of these compounds were affirmed by FT-IR and 1HNMR spectroscopy. All the synthesized compounds were assessed for their antibacterial and antifungal activities. Furthermore, a molecular docking study was conducted to elucidate the binding modes of the synthesized ligands in the active sites of Lanosterol 14-alpha demethylase (PDB ID: 5JLC) and DNA Gyrase B (PDB ID: 1AJ6), aiming to display the binding interactions and predict the mechanism of action of the synthesized ligands. Results: Five compounds (4g, 4j, 4i, 4c, and 4b) showed significant antibacterial action against gram-positive B. subitilis and gram-negative E. coli and antifungal activity against C. albicans and A. niger. Compared to the standard drugs, Chloramphenicol and Ketoconazole, molecular docking was employed to reveal how the newly synthesized ligands bind within the active pockets. The results showed that compound 4b exhibits significant antibacterial activity, while compound 4c demonstrates good antifungal activity. Conclusion: This study emphasizes the distinct structural features and notable biological activity of the synthesized compounds. In the quest for new antibacterial and antifungal agents, these compounds have the potential to offer significant benefits to society.