Alternaphenol B2, a new IDH1 inhibitor from the coral-derived fungus Parengyodontium album SCSIO SX7W11

Abstract

A new aromatic polyketide, alternaphenol B2 (1), and four known compounds (2–5) were isolated from the coral-derived fungus Parengyodontium album SCSIO SX7W11. Their structures were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy and comparison with reported literatures. Compounds 1 and 2 exhibited selective inhibitory activity against isocitrate dehydrogenase mutant R132H (IDH1m), with IC₅₀ values of 41.9 and 27.7 μM, respectively. Our findings thus provide a fresh incentive for investigation on IDH1m inhibitors as lead compounds for cancer treatment.

Graphical Abstract

Keywords:

• Coral derived fungus
• isocitrate dehydrogenase
• polyketide
• secondary metabolites

Acknowledgments

We thank the center of analytical facility at the South China Sea Institute of Oceanology, Guangzhou, China. In particular, we appreciate the help of Dr. Zhihui Xiao and Dr. Xiaohong Zheng for recording NMR data, and Ms. Aijun Sun, Ms. Yun Zhang, and Xuan Ma for acquisition of HRESIMS data.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This research was funded by Key Science and Technology Project of Hainan Province (ZDKJ202018), Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City (2021CXLH0013), National Natural Science Foundation of China (22077128, 22037006, U2106207), Guangdong Provincial Marine Economic Development (Six Major Marine Undertakings) Special Fund Project (GDNRC [2021] 54), Local Innovation and Entrepreneurship Team Project of Guangdong (2019BT02Y262) and Open Program of Shenzhen Bay Laboratory (SZBL2021080601006) and Nansha District Science and Technology award (NSJL202102).