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Accession IconGSE24584

The antitumor mechanism of Desmosdumotin C Analog

Organism Icon Homo sapiens
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Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

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In our continuing study of the desmosdumotin C (1) series, twelve new analogues, 2132, mainly with A-ring modifications, were prepared and evaluated for in vitro anticancer activity against several human tumor cell lines. Among them, the 4-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant cytotoxicity against multiple human tumor cell lines with ED50 values of 1.12.8 microM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an iso-butyl ether showed selective cytotoxicity against lung cancer A549 cells (ED50 1.7 microM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase.
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