Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines
Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines
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DOI：
10.1016/j.bmc.2005.10.038
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发表时间：
2006-03-15
影响因子：
3.5
通讯作者：
Martínez-Vázquez, M
中科院分区：
文献类型：
--
作者：
Parra-Delgado, H;Compadre, CM;Martínez-Vázquez, M
描述了 14 种银素 B (1) 类似物的合成、表征、抗癌活性和比较分子场分析 (CoMFA)。使用磺胺罗丹明 B 试验测定了银素 B 衍生物对 K562（白血病）、PC-3（前列腺）、U251（中枢神经系统）和 HCT-15（结肠）人类癌细胞系生长的影响。该系列中活性最强的化合物 2-甲酰基-(16 beta,24R)-16,24-epoxy-25-羟基环art-1-en-3-one (12) 的效力比 argentatin B (1) 强约 35-50 倍。使用 Sybyl6.9 的 3D 建模的六种衍生物的 X 射线晶体学构建结构。 K562 2 细胞系中 Log (1/IC50) 的 CoMFA 给出 q(2)=0.507、r(2)=0.907 和三个分量。标准差 CoMFA 等值线表明，活性增加与 C-2 处的大基团、C1-C2 双键和 C-25 处的低电子密度相关。银素 B 和一种衍生物的实验 Log P 值比计算的 C Log P 值亲水性高 1-2 个 Log 单位。 (c) 2005 Elsevier Ltd. 保留所有权利。
Synthesis, characterization, anticancer activity, and comparative molecular field analysis (CoMFA) of 14 argentatin B (1) analogs are described. The effect of argentatin B derivatives oil the growth of K562 (leukemia), PC-3 (prostate), U251 (CNS), and HCT-15 (colon) human cancer cell lines was determined using the sulforhodamine B test. The most active compound in this series, 2-formyl-(16 beta,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one (12), was about 35-50 times more potent than argentatin B (1). Structures were built using the X-ray crystallography of six derivatives for 3D modeling with Sybyl6.9. CoMFA of Log (1/IC50) in K562 2 cell line gave q(2)=0.507,r(2)=0.907, and three components. The standard deviation CoMFA contours indicate that increased activity is associated with a bulky group at C-2, a C1-C2 double bond, and low electronic density at C-25. Experimental Log P values for argentatin B and one derivative were 1-2 Log units more hydrophilic than the calculated C Log P values. (c) 2005 Elsevier Ltd. All rights reserved.