Recent Advances in Indole-Based Heterocyclic Compounds as Antibacterial and Antifungal Agents: Synthetic Strategies, Structure–Activity Relationships and Therapeutic Perspectives

Abstract

Antimicrobial resistance (AMR) has emerged as one of the greatest challenges to global healthcare, 
significantly reducing the effectiveness of existing antibacterial and antifungal drugs. The increasing 
prevalence of multidrug-resistant bacteria and pathogenic fungi has accelerated the search for novel 
therapeutic agents with improved efficacy and safety. Among the various heterocyclic scaffolds explored in 
medicinal chemistry, the indole nucleus has gained considerable attention because of its unique structural 
characteristics, ease of functionalization, and broad spectrum of biological activities. Indole-based 
heterocyclic compounds have demonstrated remarkable antibacterial and antifungal properties by targeting 
multiple microbial pathways, including DNA replication, cell-wall synthesis, membrane integrity, and 
ergosterol biosynthesis. Recent advances in synthetic chemistry, molecular hybridization, molecular docking, 
and computational drug design have facilitated the development of potent indole derivatives with enhanced 
pharmacological profiles. This review summarizes the chemistry of indole, major synthetic approaches, 
antimicrobial activities, structure–activity relationships (SAR), molecular docking studies, ADMET 
considerations, and future prospects for indole-based antimicrobial agents.