Rare 5/7/6-fused and sphenolobane diterpenoids with synergistic antifungal activity against Candida albicans from Strophioblachia glandulosa.

Four previously unreported 5/7/6 diterpenoids (1-4), four undescribed sphenolobane diterpenoids (7-10), and three reported derivatives (5, 6, 11) were purified from Strophioblachia glandulosa (Euphorbiaceae) and identified through various spectroscopic methods, ECD calculation, 13C NMR calculation with DP4+ analysis, and X-ray diffraction. The obtained diterpenoids were evaluated for the inhibitory activity against Candida albicans, and all the compounds demonstrated potent antifungal activity in combination with fluconazole (FLC) against drug-resistant C. albicans. Preliminary mechanism investigations revealed that the most abundant compound 6 when combined with FLC inhibited the formation of C. albicans hyphal and biofilm, disrupting the cell membrane integrity and mitochondrial function. These findings highlight the therapeutic potential of the combined optimization of the 5/7/6 diterpenoids with FLC for combating azole-resistant C. albicans infections.