Synthesis of O-Prenylated O-Glycosylated and O-Benzylated Phenazines Derivatives and Their Antimicrobial and Molecular Docking Studies.

A series of novel O-prenylated, O-glycosylated, and O-benzylated phenazine derivatives were efficiently synthesized in good yields from 5-O-methylembelin. Structures of these derivatives were confirmed by infrared, proton, and carbon-13 NMR, and mass spectral analysis. Antimicrobial evaluation against Staphylococcus aureus, Escherichia coli, and Candida albicans suggested several derivatives possessed significant activity. Specifically, compounds 4e, 6e, and 7e exhibited considerable antibacterial activity, inhibiting zones of up to 12 mm, whereas compounds 4c, 4d, 6e, and 7c possessed moderate antifungal activity (12-13 mm), compared to fluconazole (23 mm). Structure-activity relationship analysis proposes the integration of halog substituents and glycosylation leads to increased potency by increasing lipophilicity and interacting better with membranes. Molecular docking studies also confirmed these findings, revealing suitable binding affinities of the active compounds with microbial target proteins. Overall, this work offers new phenazine scaffolds potential candidates for the development of antibacterial and antifungal drugs.