1 research outputs found
Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells
Novel
carbamate (<b>7a</b>–<b>7h</b>) and carbonate
(<b>7i</b>, <b>7j</b>, and <b>8</b>) dimers of melampomagnolide
B have been synthesized by reaction of the melampomagnolide-B-triazole
carbamate synthon <b>6</b> with various terminal diamino- and
dihydroxyalkanes. Dimeric carbamate products <b>7b</b>,<b> 7c</b>, and <b>7f</b> exhibited potent growth inhibition
(GI<sub>50</sub> = 0.16–0.99 μM) against the majority
of cell lines in the NCI panel of 60 human hematological and solid
tumor cell lines. Compound <b>7f</b> and <b>8</b> exhibited
anticancer activity that was 300-fold and 1 × 10<sup>6</sup>-fold
more cytotoxic than DMAPT, respectively, at a concentration of 10
μM against rat 9L-SF gliosarcoma cells. Compounds <b>7a</b>–<b>7j</b> and <b>8</b> were also screened against
M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and
exhibited 2- to 10-fold more potent antileukemic activity against
M9-ENL1 cells (EC<sub>50</sub> = 0.57–2.90 μM) when compared
to parthenolide (EC<sub>50</sub> = 6.0) and showed potent antileukemic
activity against five primary AML cell lines (EC<sub>50</sub> = 0.76–7.3
μM)