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Design, Synthesis, And Evaluation Of A Water-soluble Antofine Analogue With High Antiproliferative And Antitumor Activity.

Yongseok Kwon, J. Song, Boeun Lee, Jinkyung In, H. Song, H. Chung, S. Lee, S. Kim
Published 2013 · Chemistry, Medicine

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New water soluble antofine C-13a analogues were designed, synthesized, and evaluated for antiproliferative activity against cancer cells. Particularly, (-)-(R)-13a-hydroxymethylantofine ((-)-(R)-4b) demonstrated notable growth inhibition against a panel of human cancer cell lines. This growth inhibition was associated with the arrest of the cell cycle in the G0/G1 phases and suppression of mTOR signaling in human lung A549 cancer cells. Compound (-)-(R)-4b also overcame paclitaxel-resistance in human lung cancer cells (A549-Pa) by suppressing P-glycoprotein expression. Furthermore, compound (-)-(R)-4b significantly inhibited the tumor growth of A549 and A549-Pa xenografts in a nude mouse model, which suggests it is a promising novel antitumor agent with sufficient aqueous solubility.
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