2. Academic Validation
  3. Butenolides from a marine-derived fungus Aspergillus terreus with antitumor activities against pancreatic ductal adenocarcinoma cells

Butenolides from a marine-derived fungus Aspergillus terreus with antitumor activities against pancreatic ductal adenocarcinoma cells

  • Bioorg Med Chem. 2018 Dec 1;26(22):5903-5910. doi: 10.1016/j.bmc.2018.10.040.
Changxing Qi 1,  Weixi Gao 1,  Danyingzi Guan 1,  Jianping Wang 1,  Mengting Liu 1,  Chunmei Chen 1,  Hucheng Zhu 1,  Yuan Zhou 1,  Yongji Lai 2,  Zhengxi Hu 3,  Qun Zhou 4,  Yonghui Zhang 5
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, People's Republic of China. Electronic address: laiyongji1024@163.com.
  • 3 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: hzx616@126.com.
  • 4 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zqtcm@163.com.
  • 5 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhangyh@mails.tjmu.edu.cn.
PMID: 30392953 DOI: 10.1016/j.bmc.2018.10.040
Abstract

Chemical study on the extract of a marine-derived fungus Aspergillus terreus yielded twelve butenolide derivatives, including three new compounds, namely asperlides A-C (1-3) and nine known butenolides (4-12). The structures of 1-3 were confirmed by comprehensive spectroscopic analysis, including HRESIMS, NMR spectroscopy, and calculated electronic circular dichroism (ECD). The cytotoxicity of the compounds was evaluated using PANC-1, HCC1806, HepG2, BEAS-2B and HT-29 Cancer cells. The results showed that (+)-3',3'-di-(dimethylallyl)-butyrolactone II (4) and versicolactone B (6) exhibited the most potent cytotoxin of PANC-1 cell line, with the IC50 values of 5.3 and 9.4 μM, respectively. Morphological features of Apoptosis were observed in 4 and 6-treated PANC-1 cells, including apoptotic body formation, membrane blebbing, cell shrinkage and nuclear condensation. Cell cycle analysis with propidium iodide staining exhibited that 4 inhibits proliferation of PANC-1 cells via the induction of G2/M and S phase arrest, while 6 could retard the PANC-1 cells via the induction of S phase arrest. Flow cytometric analysis suggested that treatment with 4 and 6 significantly induced PANC-1 cells Apoptosis. These findings indicated that 4 and 6 might serve as a starting point for the development of an Anticancer drug for the treatment of pancreatic ductal adenocarcinoma.

Keywords

Antitumor; Aspergillus terreus; Butenolides; Marine-derived fungi; Pancreatic ductal adenocarcinoma.

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