Grincamycins P–T: Rearranged Angucyclines from
the Marine Sediment-Derived Streptomyces sp. CNZ-748
Inhibit Cell Lines of the Rare Cancer Pseudomyxoma Peritonei
posted on 2021-04-26, 12:36authored byZhuo Shang, Zachary E. Ferris, Douglas Sweeney, Alexander B. Chase, Chunhua Yuan, Yvonne Hui, Lukuan Hou, Ethan A. Older, Dan Xue, Xiaoyu Tang, Weipeng Zhang, Prakash Nagarkatti, Mitzi Nagarkatti, Traci L. Testerman, Paul R. Jensen, Jie Li
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 Streptomyces sp. 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, Streptomyces sp. CNZ-748, and compared the BGCs detected with those linked to
the production of angucyclines with different aglycon structures.