Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Ukraine, Lviv, Ukraine.
Arch Pharm (Weinheim). 2011 Aug;344(8):514-22. doi: 10.1002/ardp.201100055. Epub 2011 Jun 16.
The synthesis and antitumor activity screening of novel isatin based conjugates with thiazolidine and pyrazoline moieties were performed. Reaction of 3,5-diaryl-4,5-dihydropyrazoles with chloroacetyl chloride yielded starting 2-chloro-1-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-ethanones which were utilized in alkylation of isatin and 5-bromoisatin. Thus, corresponding 1-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-2-oxoethyl]-1H-indole-2,3-diones (1a-1d) have been obtained. The compounds 1a-1d have been used in Knoevenagel condensation with 4-thiazolidinones for obtaining a series of 5-ylidenederivatives 2a-2f and 3a-3d. The synthesized compounds were tested for their anticancer activity in NCI60 cell lines. Among the tested compounds, 5-bromo-1-{2-[5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl]-2-oxoethyl}-1H-indole-2,3-dione (1d) was found to be the most active candidate with selective influence on leukemia subpanel tumor cell lines with GI(50) values range of 0.69-3.35 µM.
新型含噻唑烷和吡唑啉结构的靛红类化合物的合成及抗肿瘤活性筛选。3,5-二芳基-4,5-二氢吡唑与氯乙酰氯反应生成起始的 2-氯-1-(3,5-二芳基-4,5-二氢吡唑-1-基)-乙酮，可用于靛红和 5-溴靛红的烷基化反应。因此，得到了相应的 1-[2-(3,5-二芳基-4,5-二氢吡唑-1-基)-2-氧代乙基]-1H-吲哚-2,3-二酮（1a-1d）。化合物 1a-1d 与 4-噻唑烷酮进行 Knoevenagel 缩合，得到一系列 5-亚甲基衍生物 2a-2f 和 3a-3d。合成的化合物在 NCI60 细胞系中进行了抗肿瘤活性测试。在所测试的化合物中，5-溴-1-{2-[5-(4-氯苯基)-3-(4-甲氧基苯基)-4,5-二氢吡唑-1-基]-2-氧代乙基}-1H-吲哚-2,3-二酮（1d）是最活跃的候选物，对白血病亚系肿瘤细胞系具有选择性影响，GI(50)值范围为 0.69-3.35µM。
