Recent Developments on Coumarin Hybrids as Antimicrobial Agents

<b>Introduction</b>: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious threat to public health. Coumarin is a naturally occurring compound contributing health-beneficial features in drug discovery. Its high solubility in organic solvents, high bioavailability, simple structure, low toxicity, and low molecular weight make it an ideal candidate for combining with other pharmacophores to develop new therapeutic agents. This compound exhibits several biological activities, including antimicrobial, anticancer, anti-inflammatory, antidiabetic, neuroprotective, and anticoagulant effects, motivating medicinal researchers to hybridize it with other compounds to enhance its pharmacological efficacy. Hybridization of different pharmacophores via suitable linkers, including cleavable and non-cleavable ones, is a promising approach in drug development, resulting in new therapeutics with improved biological activity. Therefore, the hybridization of coumarin with other pharmacophores has become an interesting paradigm for medicinal scientists. Aim: This review aims to summarize the existing scientific literature on coumarin-based hybrid compounds with antimicrobial capabilities and discuss the structure-activity relationship (SAR) of these hybrids to potentially guide future research on and development of coumarin-based drugs for microbial treatment. <b>Material and Methods</b>: The review focuses on open-access literature about coumarin hybrid drugs available through searching tools such as Google, Google Scholar, ScienceDirect, and Scopus, published from 2024 to 2025. <b>Results</b>: Coumarin hybrids exhibit promising antimicrobial activity, particularly against <i>S. aureus</i> and <i>C. albicans</i>. The SAR reveals that halogenation, bulky aromatics, nitro, and hydroxyl groups enhance the interaction of the coumarin rings with amino acid residues. <b>Conclusions</b>: The reported coumarin hybrids showed a promising antimicrobial activity, with structural modifications influencing their activity. Hence, more studies, including more pre-clinical and clinical evaluations, are recommended for these hybrid compounds.