Grincamycins P–T: Rearranged Angucyclines from the Marine Sediment-Derived Streptomycessp. CNZ-748 Inhibit Cell Lines of the Rare Cancer Pseudomyxoma Peritonei

Autor: Shang, Zhuo, Ferris, Zachary E., Sweeney, Douglas, Chase, Alexander B., Yuan, Chunhua, Hui, Yvonne, Hou, Lukuan, Older, Ethan A., Xue, Dan, Tang, Xiaoyu, Zhang, Weipeng, Nagarkatti, Prakash, Nagarkatti, Mitzi, Testerman, Traci L., Jensen, Paul R., Li, Jie
Zdroj: Journal of Natural Products; May 2021, Vol. 84 Issue: 5 p1638-1648, 11p
Abstrakt: While marine natural products have been investigated for anticancer drug discovery, they are barely screened against rare cancers. Thus, in our effort to discover potential drug leads against the rare cancer pseudomyxoma peritonei (PMP), which currently lacks effective drug treatments, we screened extracts of marine actinomycete bacteria against the PMP cell line ABX023-1. This effort led to the isolation of nine rearranged angucyclines from Streptomycessp. CNZ-748, including five new analogues, namely, grincamycins P–T (1–5). The chemical structures of these compounds were unambiguously established based on spectroscopic and chemical analyses. Particularly, grincamycin R (3) possesses an S-containing α-l-methylthio-aculose residue, which was discovered in nature for the first time. All of the isolated compounds were evaluated against four PMP cell lines and some exhibited low micromolar inhibitory activities. To identify a candidate biosynthetic gene cluster (BGC) encoding the grincamycins, we sequenced the genome of the producing strain, Streptomycessp. CNZ-748, and compared the BGCs detected with those linked to the production of angucyclines with different aglycon structures.
Databáze: Supplemental Index