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Published on: September 5, 2018
Ferroptosis-inhibitory compounds from the deep-sea-derived Penicillium sp
Xiao-Wei Zhao1, Zheng-Biao Zou2, Ying-Ying Lin3
1Hainan Academy of Medical Sciences, Hainan Medical University, 3 Xueyuan Road, Haikou 571199, China; School of Traditional Chinese Materia Medical, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.
None:
Two new citrinin analogues (1 and 10) and one new xanthone (17) were isolated from the deep-sea-derived fungus Penicillium sp. 3A00398, along with 55 known compounds. The structures of the new compounds were determined by comprehensive spectroscopic analysis and TD-DFT-based ECD calculations. All isolated compounds were evaluated for their protective effects against RSL3-induced ferroptosis. Penicitrinols Q (1) and B (2), citrinin H1 (4), sclerotinin A (7), 3-hydroxy microxanthone (19), sydowinin A (23), and 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran (40) exhibited significant effect, with EC₅₀ values below 10 μM. Notably, penicitrinol Q demonstrated the most potent activity, with an EC₅₀ value of 0.48 μM. Further mechanistic investigation revealed that penicitrinol Q exerts the protective role by modulating the expression of the HO-1 gene. This study identifies novel ferroptosis inhibitors and provides new insights into potential therapeutic strategies for ferroptosis-related diseases.
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