Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity
Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity
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DOI：
10.1021/jm300789g
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发表时间：
2012-10-25
影响因子：
7.3
通讯作者：
Lesyk, Roman
中科院分区：
文献类型：
--
作者：
Havrylyuk, Dmytro;Zimenkovsky, Borys;Lesyk, Roman
对新型化合物3-[2-(3，5-二芳基-4)，S-dihydropyrazol-1-yl)-4-oxo-4，5-dihydro-1，3-thiazol-5-ylidene]-2，3-dihydro-1H-indol-2-ones 1-23和3-(3，5-diarylpyrazol-1-yl)-2，3-dihydro-1H-indol-2-ones 24-39]进行了合成和抗肿瘤活性筛选。国家癌症研究所对所合成化合物的体外抗癌活性进行了检测。它们对白血病、黑色素瘤、肺癌、结肠癌、中枢神经系统、卵巢癌、肾癌、前列腺癌和乳腺癌等多种肿瘤细胞株均表现出一定的抗癌活性。讨论了构效关系。最有效的抗癌化合物10的平均GI(50)和TGI值分别为0.071和0.76mU/M。对非小细胞肺癌细胞株HOP-92(GI(50)=0.01mU M)、结肠癌细胞株HCT-116(GI(50)=0.018 mU M)、中枢神经系统癌细胞株SNB-75(GI(50)=0.0159 mU M)、卵巢癌细胞株NCI/ADR-RES(GI(50)=0.0169 mU M)、肾癌细胞株RXF393(GI(50)=0.0197 mU M)显示出最强的抗增殖作用。
The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,S-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 GI(50) and TGI values of 0.071 mu M and 0.76 mu M, respectively. It demonstrated the highest antiproliferative influence on the non-small-cell lung cancer cell line HOP-92 (GI(50) < 0.01 mu M), colon cancer line HCT-116 (GI(50) = 0.018 mu M), CNS cancer cell line SNB-75 (GI(50) = 0.0159 mu M), ovarian cancer cell line NCI/ADR-RES (GI(50) = 0.0169 mu M), and renal cancer cell line RXF 393 (GI(50) = 0.0197 mu M).