An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins
An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins
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DOI：
10.1021/jm0704189
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发表时间：
2007-10-18
影响因子：
7.3
通讯作者：
Bremner, John B.
中科院分区：
文献类型：
--
作者：
Vine, Kara L.;Locke, Julie M.;Bremner, John B.
A range of substituted N-alkylisatins were synthesized and their cytotoxicity evaluated against several cancer cell lines in vitro. SAR studies indicated that the introduction of an aromatic ring with a one or three carbon atom linker at NI enhanced the activity from that of the allyl, 2'-methoxyethyl, and 3'-methylbutyl N-substituted isatins. Furthermore, electron-withdrawing groups substituted at the meta or para position of the ring were favored over the ortho orientation. Of the 24 compounds screened, nine displayed sub-micromolar IC50 values and in general demonstrated greater selectivity toward leukemia and lymphoma cell lines over any of the carcinoma cell lines tested. 5,7-Dibromo-N-(p-methylbenzyl)isatin (6) was the most active compound, inhibiting the metabolic activity of both U937 and Jurkat cancer cell lines at 0.49 mu M. Various N-alkylisatins were also found to dramatically alter lymphocyte morphology, destabilize microtubules, inhibit tubulin polymerization, induce G2/M cell cycle arrest, and activate the effector caspase-3 and -7.
