A comprehensive review of indole hybrids as anti-bacterial and anti-fungal agents: synthetic protocols and SAR studies

Antimicrobial resistance, a consequence of the prevalent overuse and misuse of antibiotics, has become a serious global health concern. While extensive drug discovery efforts are constantly underway to combat this, the relentless emergence of resistant pathogens demands innovative strategies beyond traditional approaches to address this pervasive health crisis. Among promising strategies, such as drug repurposing and novel chemotype development, molecular hybridization, particularly involving the versatile indole heterocycle, stands out. Its inherent structural flexibility offers unique avenues for optimizing pharmacokinetics, boosting biological activity, and enabling potent bioisosteric modifications. This review consolidates and analyzes advances in indole-based derivatives reported between 2017 and 2025, specifically as antibacterial and antifungal agents. Beyond simply listing advances, we critically integrated chemical synthesis with structure-activity relationships (SAR) and their associated biological activity emerging from a broad spectrum of indole-based modifications. By rigorously detailing these insights, we specifically aim to guide and accelerate the rational design of novel indole-based molecules, providing a vital framework for developing the next generation of antimicrobials to overcome emerging resistance mechanisms.