Cytotoxic Terpenoids from a Soil-Derived Fungus Aspergillus Calidoustus

Abstract

Fifteen terpenoid derivatives, including six new sesquiterpenoids (1 – 5 and 10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known compounds (6 – 9 and 12 – 14) were isolated and characterized from fungus Aspergillus calidoustus, which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 15 was a rare austin analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected furan ring. Their structures were established by means of spectroscopic methods and single-crystal X-ray diffraction. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC₅₀ values of 5.54 and 9.78μM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function.

Note:
Funding Information: This research was funded by the Program for the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), the Fundamental Research Funds for the Central Universities (No. 2020kfyXJJS083), the National Key R&D Program of China (No. 2021YFA0910500), and the Research and Development Program of Hubei Province (No. 2020BCA058).

Declaration of Interests: The authors of the present manuscript have declared that no competing interests exist.

Keywords: Soil-Derived Fungus, Aspergillus calidoustus, terpenoids, cytotoxicity