Characterization of novel synthesized small molecular compounds against non-small cell lung cancer.
Characterization of novel synthesized small molecular compounds against non-small cell lung cancer.
复制标题
DOI：
10.1016/j.athoracsur.2011.04.081
复制
发表时间：
2011-09
影响因子：
4.6
通讯作者：
Lau, Christine L.
中科院分区：
文献类型：
--
作者：
Zhao, Yunge;Turlington, Mark;LaPar, Damien J.;Jones, David R.;Harris, David A.;Kron, Irving L.;Pu, Lin;Lau, Christine L.
除手术外，标准铂类化疗药物是非小细胞肺癌（NSCLC）的首选治疗方法;然而，几乎没有改善（5年生存率）。因此，非常需要开发用于NSCLC治疗的创新治疗剂。开发了高对映选择性的合成方法，建立了广泛的化合物库。细胞毒性、细胞敏感性、细胞增殖、细胞侵袭和三维集落形成测定用于评估这些化合物在非小细胞肺癌（NSCLC）细胞系中的抗癌潜力。我们发现化合物PL 54的S-形式（PL 54 S，5-20 μM）在5种测试的NSCLC细胞系中表现出强的抗癌活性。我们进一步合成了高纯度的PL 54的R型对映体（PL 54 R）及其外消旋体（PL 54 Rac），并表征了它们的抗癌活性。结果表明，PL 54 S比PL 54 R和PL 54 Rac对测试的细胞系更有效。此外，在正常人肺成纤维细胞中观察到较少的细胞毒性。类似地，与PL 54 R和PL 54 Rac相比，PL 54 S显示出更大的抗集落形成活性。细胞敏感性测定显示，与PL 54 R和二甲亚砜对照相比，PL 54 S和PL 54 Rac显著抑制集落形成（p < 0.01）。所有PL 54化合物（5至20 μM）均显著抑制A549细胞系的细胞增殖和侵袭（p < 0.01）。软琼脂集落形成测定显示，PL 54 S和PL 54 Rac（10 mM）而不是PL 54 R显著抑制测试的NSCLC细胞的集落形成（p < 0.01）。立体特异性化合物可能被证明是治疗NSCLC的新技术。
With the exception of surgery, the standard platinum-based chemotherapeutic agents are the preferred treatment for non-small cell lung cancer (NSCLC); however little improvement (5-year survival) has been made. Therefore it is highly desirable to develop innovative therapeutic agents for NSCLC treatment. Highly enantioselective synthetic methods were developed and a broad compound library was established. Cell toxicity, cell sensitivity, cell proliferation, cell invasion, and three-dimensional colony formation assays were used to assess the anticancer potential of these compounds in non–small-cell lung cancer (NSCLC) cell lines. We found that the S-form of compound PL54 (PL54S, 5–20 µM) exhibited strong anticancer activity in 5 tested NSCLC cell lines. We further synthesized a highly pure R-form enantiomer of PL54 (PL54R) and its race-mate (PL54Rac) and characterized their anticancer activities. The results showed that PL54S is more potent than PL54R and PL54Rac against the tested cell lines. Furthermore, less cellular toxicity was observed in the normal human lung fibroblasts. Similarly, PL54S displayed greater anti–colony formation activity compared with PL54R and PL54Rac. The cellular sensitivity assay revealed that PL54S and PL54Rac significantly suppressed cologenic formation compared with PL54R and dimethyl sulfoxide controls (p < 0.01). All PL54 compounds (5 to 20 µM) significantly inhibited cell proliferation and invasion of the A549 cell line (p < 0.01). A soft agar colony formation assay revealed that PL54S and PL54Rac (10 mM), but not PL54R, significantly inhibited colony formation of tested NSCLC cells (p < 0.01). The stereospecific compounds may prove to be a novel technique for the treatment of NSCLC.
登录
查看更多内容
影响因子：
254.7
作者：
Landis, SH;Murray, T;Wingo, PA
通讯作者：
Wingo, PA
影响因子：
2.9
作者：
Skibo, EB;Xing, CG
通讯作者：
Xing, CG
影响因子：
5.2
作者：
Turlington, Mark;DeBerardinis, Albert M.;Pu, Lin
通讯作者：
Pu, Lin
影响因子：
11.5
作者：
Ma, PC;Schaefer, E;Salgia, R
通讯作者：
Salgia, R
Treosulfan的DNA烷基化和链间交联。
影响因子：
8.8
作者：
Hartley, J A;O'Hare, C C;Baumgart, J
通讯作者：
Baumgart, J