BODIPY conjugates with monoterpenoids for photodynamic diagnostics and therapy: Design, spectral properties, photostability and antifungal activity

The development of BODIPY-based theranostic agents for photodynamic inactivation (PDI) of pathogens is one of the rapidly developing areas. In this work, we present the results of the synthesis of the diiodo-BODIPY with methanol, (+)-myrtenol and thiotherpenoid conjugates. We performed a comparative analysis of the influence of the ester residue nature, iodination, and solvent properties on the spectral, generation characteristics and photostability of the alkyl- and diiodo-BODIPY conjugates, and their efficiency to penetrate and inhibit Candida albicans cells under light. Non-halogenated conjugates of BODIPY with methanol, (+)-myrtenol and thiotherpenoid show potential for fluorescence diagnostics due to their high fluorescence, photostability, and membranotropicity. Diiodo-substituted terpene-BODIPY conjugates have higher singlet oxygen generation efficiency and greater affinity for lipid biostructures compared to non-halogenated analogues. Furthermore, halogenation and conjugation of BODIPY to a monoterpenoid modify the preferred biotarget and contribute to the effective inhibition of Candida albicans viability. These results suggest that diiodo-substituted terpene-BODIPY conjugates may be promising antifungal agents for blocking fungal virulence.