Absolute Stereochemistry and Cytotoxic Effects of Vismione E from Marine Sponge-Derived Fungus Aspergillus sp. 1901NT-1.2.2
Elena V. Girich, Phan Thi Hoai Trinh, Liliana E. Nesterenko, Roman S. Popov, Natalya Yu. Kim, Anton B. Rasin, Ekaterina S. Menchinskaya, Aleksandra S. Kuzmich, Ekaterina A. Chingizova, Артем С. Минин, Ngo Thi Duy Ngoc, Trần Thị Thanh Vân, Ekaterina A. Yurchenko, Anton N. Yurchenko, Dmitry V. Berdyshev
Abstract
The metabolic profile of the Aspergillus sp. 1901NT-1.2.2 sponge-associated fungal strain was investigated using the HPLC MS technique, and more than 23 peaks in the HPLC MS chromatogram were detected. Only two minor peaks were identified as endocrocin and terpene derivative MS data from the GNPS database. The main compound was isolated and identified as known anthraquinone derivative vismione E. The absolute stereochemistry of vismione E was established for the first time using ECD and quantum chemical methods. Vismione E showed high cytotoxic activity against human breast cancer MCF-7 cells, with an IC50 of 9.0 µM, in comparison with low toxicity for normal human breast MCF-10A cells, with an IC50 of 65.3 µM. It was found that vismione E inhibits MCF-7 cell proliferation and arrests the cell cycle in the G1 phase. Moreover, the negative influence of vismione E on MCF-7 cell migration was detected. Molecular docking of vismione E suggested the IMPDH2 enzyme as one of the molecular targets for this anthraquinone derivative.