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Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells
A series of novel, heteroaryl carboxylic acid conjugates of the sesquiterpene melampomagnolide-B (MMB, 3) has been evaluated as antitumor agents against an NCI panel of 64 human hematopoetic and solid tumor cell lines. The indole-3-acrylic acid conjugate 7j and the indole-3-carboxylic acid conjugate 7k were found to be the most potent analogs in the series. Compounds 7j and 7k exhibited remarkable growth inhibition, with GI50 values in the range 0.03?0.30?muM and 0.04?0.28?muM, respectively, against the cell lines in the leukemia sub-panel, and GI50 values of 0.05?0.40?muM and 0.04?0.61?muM, respectively, against 90% of the solid tumor cell lines in the NCI panel. Compound 7a was particularly effective against the sub-panel of breast cancer cell lines with GI50 values in the range <0.01?0.30?muM. Compounds 7j, 7a and its water soluble analog 7p also exhibited potent anticancer activity against rat 9L-SF gliosarcoma cells in culture. Compound 7j was the most potent compound in the series in the M9-ENL1 AML cell assay with a lethal dose concentration EC50 value of 720?nM, and exhibited the greatest cytotoxicity against a collection of primary AML stem cell specimens, which included a specimen that was unresponsive to PTL, affording EC50 values in the range 0.33?1.0?muM in three out of four specimens. The results from this study provide further evidence that analogs of the sesquiterpene MMB can be designed to afford molecules with significantly improved anticancer activity. Thus, both 7j and 7k are considered potential lead molecules in the search for new anticancer agents that can be used as treatments for both hematopoetic and solid tumors. Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.name: Benzofuran-2-carboxylic acid, you can also check out more blogs about496-41-3
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Benzofuran – Wikipedia,
Benzofuran | C8H1745O – PubChem