Synthesis and Antimicrobial Evaluation of Chroman-4-One and Homoisoflavonoid Derivatives

The continuous increase in microbial resistance to therapeutic agents has become one of the greatest challenges to global health. In this context, the present study investigated the bioactivity of 25 chroman-4-one and homoisoflavonoid derivatives-17 of which are novel-against pathogenic microorganisms, including <i>Staphylococcus epidermidis</i>, <i>Pseudomonas aeruginosa</i>, <i>Salmonella enteritidis</i>, <i>Candida albicans</i>, <i>C. tropicalis</i>, <i>Nakaseomyces glabratus</i> (formerly <i>C. glabrata)</i>, <i>Aspergillus flavus</i>, and <i>Penicillium citrinum</i>. Antimicrobial assay was performed using the microdilution technique in 96-well microplates to determine the minimum inhibitory concentration (MIC). Thirteen compounds exhibited antimicrobial activity, with compounds <b>1</b>, <b>2</b>, and <b>21</b> demonstrating greater potency than the positive control, especially against <i>Candida</i> species. Molecular modeling suggested distinct mechanisms of action in <i>Candida albicans</i>: <b>1</b> potentially inhibits cysteine synthase, while <b>2</b> and <b>21</b> possibly target HOG1 kinase and FBA1, key proteins in fungal virulence and survival. Our findings indicated that the addition of alkyl or aryl carbon chains at the hydroxyl group at position 7 reduces antimicrobial activity, whereas the presence of methoxy substituents at the <i>meta</i> position of ring B in homoisoflavonoids enhances bioactivity. These findings highlight key structural features of these compound classes, which may aid in the development of new bioactive agents against pathogenic microorganisms.