Exploration of Sapogenins as Promising Lead Compounds in the Development of Novel Antimicrobial Agents

ABSTRACT Sapogenins, the aglycone moieties of saponins, have garnered interest for their potential as antimicrobial agents due to their membrane‐disrupting properties. This study investigates a selection of natural and semi‐synthetic derivatives of two key sapogenins, diosgenin and tigogenin, to evaluate their antimicrobial efficacy against Escherichia coli and Pseudomonas aeruginosa . A series of derivatives with modifications at the C‐3 position were synthesised and tested for their effects on bacterial growth, carbon metabolism, and membrane disruption. Results from microbial growth assays identified pseudo‐diosgenin and (25 R )‐5α‐spirostan‐3β‐yl l ‐glutamate as the most effective inhibitors of E. coli , while P. aeruginosa showed high sensitivity to (25 R )‐spirost‐5‐en‐3β‐yl pyridine‐3‐carboxylate and pseudo‐diosgenin. The EcoPlate assays demonstrated compound‐specific inhibition of bacterial metabolism, particularly by diosgenin ((25 R )‐spirost‐5‐en‐3β‐yl ( E )‐3‐(3,4‐dihydroxyphenyl)acrylate) and pseudo‐diosgenin ((25 R )‐furost‐5‐en‐3β‐acetoxy‐26‐ol), highlighting disruptions in key pathways such as carbohydrate and phenolic compounds metabolism. These findings underscore the potential of sapogenins, particularly modified derivatives, as promising leads in the development of novel antimicrobial therapies.