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J Nat Prod. 2019 Apr 26;82(4):970-979. doi: 10.1021/acs.jnatprod.8b01033. Epub 2019 Mar 7.

Fuscasins A-D, Cycloheptapeptides from the Marine Sponge Phakellia fusca.

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Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200127 , People's Republic of China.
School of Pharmaceutical Sciences , Xiamen University , South Xiangan Road , Xiamen , Fujian 361102 , People's Republic of China.
School of Traditional Chinese Materia Medica , Shenyang Pharmaceutical University , Shenyang 110016 , People's Republic of China.


Four new cycloheptapeptides, fuscasins A-D (1-4), were isolated from the marine sponge Phakellia fusca collected from the South China Sea. Their planar structures were fully characterized by spectroscopic methods, and the absolute configurations of amino acid residues were determined using the advanced Marfey's method. Structurally, 1 is a unique cycloheptapeptide with a backbone bearing a pyrrolidine-2,5-dione unit. Among the isolated compounds, 1 exhibited potent growth-inhibitory activity against HepG2 cells with an IC50 value of 4.6 μM, whereas it did not show apparent inhibitory effects against the other five human cancer cell lines, MCF-7, HeLa, NCI-H460, PC9, and SW480. Encouragingly, 1 exhibited no cytotoxicity against nonmalignant cells even with a concentration up to 100 μM. These findings suggest that 1 may display a selective inhibitory effect on the growth of HepG2 cells.

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