Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv 79010, Ukraine.
J Med Chem. 2012 Oct 25;55(20):8630-41. doi: 10.1021/jm300789g. Epub 2012 Oct 9.
The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H-indol-2-ones 1-23 and 3-(3,5-diarylpyrazol-1-yl)-2,3-dihydro-1H-indol-2-ones 24-39 are performed. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute. Most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines. The structure-activity relationship is discussed. The most effective anticancer compound 10 was found to be active with mean GI₅₀ and TGI values of 0.071 μM and 0.76 μM, respectively. It demonstrated the highest antiproliferative influence on the non-small-cell lung cancer cell line HOP-92 (GI₅₀ < 0.01 μM), colon cancer line HCT-116 (GI₅₀ = 0.018 μM), CNS cancer cell line SNB-75 (GI₅₀ = 0.0159 μM), ovarian cancer cell line NCI/ADR-RES (GI₅₀ = 0.0169 μM), and renal cancer cell line RXF 393 (GI₅₀ = 0.0197 μM).
新型 3-[2-(3,5-二芳基-4,5-二氢吡唑-1-基)-4-氧代-4,5-二氢-1,3-噻唑-5-亚基]-2,3-二氢-1H-吲哚-2-酮 1-23 和 3-(3,5-二芳基吡唑-1-基)-2,3-二氢-1H-吲哚-2-酮 24-39 的合成及抗肿瘤活性筛选。采用国立癌症研究所的方法对合成化合物进行体外抗癌活性测试。其中大部分对白血病、黑色素瘤、肺癌、结肠癌、中枢神经系统癌、卵巢癌、肾癌、前列腺癌和乳腺癌细胞系具有抗癌活性。讨论了构效关系。发现最有效的抗癌化合物 10 的 GI₅₀ 和 TGI 值分别为 0.071 μM 和 0.76 μM，对非小细胞肺癌细胞系 HOP-92（GI₅₀ < 0.01 μM）、结肠癌 HCT-116（GI₅₀ = 0.018 μM）、中枢神经系统癌细胞系 SNB-75（GI₅₀ = 0.0159 μM）、卵巢癌细胞系 NCI/ADR-RES（GI₅₀ = 0.0169 μM）和肾癌细胞系 RXF 393（GI₅₀ = 0.0197 μM）具有最高的增殖抑制作用。
