New ionic derivatives of betulinic acid as highly potent anti-cancer agents.
New ionic derivatives of betulinic acid as highly potent anti-cancer agents.
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DOI：
10.1016/j.bmcl.2011.12.102
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发表时间：
2012-02-15
影响因子：
2.7
通讯作者：
Bose, Himangshu S.
中科院分区：
文献类型：
--
作者：
Suresh, Challa;Zhao, Hua;Gumbs, Angelique;Chetty, Chellu S.;Bose, Himangshu S.
白桦酸是一种天然化合物，对多种癌细胞具有较高的体外细胞毒性。然而，该化合物的水溶性较差，阻碍了有效的体内癌症研究。我们制备了新的离子衍生物的白桦酸具有更高的水溶性，而不失去该化合物的结构完整性和功能。因此，这些新的离子衍生物对不同的癌细胞系如黑色素瘤A375、神经母细胞瘤SH-SY5Y和乳腺腺癌MCF7显示出更高的抑制作用。对于A375细胞系，衍生物5的IC50值较低，为36 μM（白桦酸的IC50值为154 μM）；对于MCF7细胞系，衍生物5的IC50值也很低，为25 μM（而白桦酸的IC50值为112 μM）。这些新衍生物的高细胞毒性可能与它们大大改善的水溶性有关。我们的分析方法使用少量DMSO来帮助这些衍生物的溶解，以证明改善水溶性的优势，并模拟体内研究条件。基于MTT和LDH测定方法的细胞活力研究证实了我们的白桦酸离子衍生物（特别是4和5）对不同癌细胞的高抑制作用。
Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC50 value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC50 value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.
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