Steroids from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475 Induced Apoptosis via Retinoid X Receptor (RXR)-α Pathway
Chun-Lan Xie,
Duo Zhang,
Jin-Mei Xia,
Chao-Chao Hu,
Ting Lin,
Yu-Kun Lin,
Guang-Hui Wang,
Wen-Jing Tian,
Zeng-Peng Li,
Xiao-Kun Zhang,
Xian-Wen Yang,
Hai-Feng Chen
Affiliations
Chun-Lan Xie
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Duo Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Jin-Mei Xia
Key Laboratory of Marine Biogenetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen 361005, China
Chao-Chao Hu
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Ting Lin
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Yu-Kun Lin
Key Laboratory of Marine Biogenetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen 361005, China
Guang-Hui Wang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Wen-Jing Tian
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Zeng-Peng Li
Key Laboratory of Marine Biogenetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen 361005, China
Xiao-Kun Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Xian-Wen Yang
Key Laboratory of Marine Biogenetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen 361005, China
Hai-Feng Chen
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen 361005, China
Five new ergostanes, penicisteroids D−H (1−5), were isolated from the liquid culture of the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, along with 27 known compounds. The structures of the new steroids were established mainly on the basis of extensive analysis of 1D and 2D NMR as well as HRESIMS data. Moreover, the absolute configurations of 1 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds 2 and 4–7 showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC50 values of around 5 μM. Compounds 2 and 6, potent RXRα binders with Kd values of 13.8 and 12.9 μM, respectively, could induce apoptosis by a Retinoid X Receptor (RXR)-α-dependent mechanism by regulating RXRα transcriptional expression and promoting the poly-ADP-ribose polymerase (PARP) cleavage. Moreover, they could inhibit proliferation by cell cycle arrest at the G0/G1 phase.
