ArrayExpress Uploader0human4′-iodo-3,3,5-tripropyl-4-methoxycontrol3829arrayexpress_sid4In our continuing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, mainly with A-ring modifications, were prepared...E-GEOD-24584/profile/8773/arrayexpressuploader12cancercellchromosomegenomelinelunglung cancerspindleDec.12, 2014Falsethe-antitumor-mechanism-of-desmosdumotin-c-analogE-GEOD-24584_A-AFFY-44The antitumor mechanism of Desmosdumotin C AnalogSep.15, 2014In our continuing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, 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 1.1–2.8 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. We used microarrays to elucidate the underlying antitumor mechanism induced by Desmosdumotin C Analog Analogue 3 showed potent cytotoxicity against the highly invasive non-small-cell lung cancer cell line CL1-5 with an ED50 value of 0.11 µM. To determine which genes were differentially expressed upon CL1-5 treatment with analogue 3, the genome-wide mRNA expression profiles of 3-treated cells and control cells were determined using Affymetrix human genome U133 plus 2.0 GeneChip according to the Manufacturer’s protocolshttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-24584http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-24584/samples/