Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells

European Journal of Medicinal Chemistry
Shobanbabu BommaganiPeter A Crooks

Abstract

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 μM and 0.04-0.28 μM, respectively, against the cell lines in the leukemia sub-panel, and GI50 values of 0.05-0.40 μM and 0.04-0.61 μM, 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 μM. 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 EC...Continue Reading

Citations

Nov 26, 2019·Natural Product Reports·Robert R A FreundHans-Dieter Arndt
Oct 9, 2018·Drug Development Research·Gauri LamtureMichael J Borrelli
Aug 20, 2018·European Journal of Medicinal Chemistry·Venumadhav JanganatiPeter A Crooks
Dec 2, 2021·Journal of Medicinal Chemistry·Xingchen LiuLingyi Kong

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