Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2: an SAR study.

Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2: an SAR study.
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DOI:
10.1016/j.bmcl.2011.06.005
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发表时间:
2011-08-01
影响因子:
2.7
通讯作者:
Harding, Wayne W.
Harding, Wayne W.
中科院分区:
医学4区
文献类型:
--
作者:
Ponnala, Shashikanth;Chaudhary, Sandeep;Gonzalez-Sarrias, Antonio;Seeram, Navindra P.;Harding, Wayne W.

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在MTS细胞毒性试验中评价了一系列与domesticine和nantenine结构相关的合成阿朴啡衍生物(A环、N6环和C环截短的类似物)对人结肠癌细胞系HCT-116和Caco-2的细胞毒性。通常,环A的C1位容许烷氧基取代基以及苯甲酰基酯官能团。评价的其他修饰导致细胞毒性活性降低。鉴定的最有效化合物的IC 50值在23μM-38μM范围内,与已知的细胞毒性剂依托泊苷相当。
A series of synthetic aporphine derivatives structurally related to domesticine and nantenine (ring A, N6 and ring C truncated analogs), was evaluated in MTS cytotoxicity assays against the human colon cancer cell lines, HCT-116 and Caco-2. In general, the C1 position of ring A is tolerant of alkoxy substituents as well as a benzoyl ester functionality. Other modifications evaluated resulted in a decrease in cytotoxic activity. The most potent compounds identified had IC50 values in the range 23μM-38μM, comparable to the known cytotoxic agent, etoposide.
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