Senkyunolide B exhibits broad-spectrum antifungal activity against plant and human pathogenic fungi via inhibiting spore germination and destroying the mature biofilm.

Background: Aspergillus infection seriously jeopardizes the health and safety of life of immunocompromised patients. The emergences of antifungal resistance highlight a demand to find new effective antifungal drugs. Angelica sinensis is a medicine-food herb and phthalides are its characteristic components. A few of the phthalides have been reported to display satisfactory antifungal activities against plant pathogenic fungi. However, the structure-activity relationships and antifungal action mechanism of phthalides remain to be further explored and elucidated.

Results: The antifungal activities of five natural phthalides and four artificial analogs were investigated, and their structure-activity relationships were preliminarily elucidated in the current study. The benzene ring moiety played an essential role in their antifungal activities; the oxygen-containing substituents on the benzene ring obviously impacted their activities, the free hydroxyl was favorable to the activity. Typical phthalide senkyunolide B (SENB) exhibited broad antifungal activities against human and plant pathogenic fungi, especially, Aspergillus fumigatus. SENB affected the spore germination and hyphae growth of Aspergillus fumigatus via down-regulating phosphatidylinositol-PKC-calcineurin axis and the expression of ENG genes. Moreover, SENB disturbed the oxidation-reduction process in Aspergillus fumigatus to destroy the mature biofilms. In vivo experiments indicated SENB significantly prolonged survival and decreased fungal burden in mouse model of invasive pulmonary aspergillosis.

Conclusions: Phthalides could be considered as the valuable leads for the development of antifungal drug to cure plant and human disease. © 2023 Society of Chemical Industry.