In our efforts to develop effective treatment agents for cancer, a series of novel compounds based on 3-(1H-indol-3-yl)-1H-pyrazole scaffold and three common pharmacophores, namely thiazolidine, 1,3,4-oxadiazole, and acylpyrazole, were synthesized and evaluated for their cytotoxic activity against four human cancer cell lines. Among compounds 2a–2c and 3a–3c containing thiazolidine moiety, 2b and 3c showed moderate cytotoxic activity toward Ho-8910. The dramatic enhancement in cytotoxic activity was observed upon the introduction of a 1,3,4-oxadiazole-2-thiol moiety on 3-(1H-indol-3-yl)-1H-pyrazole scaffold. Compound 5a was the most effective against KG-1 with IC50 = 6.09 μM, which was comparable to the reference drug doxorubicin. Compound 5b was potent against HepG-2 (IC50 = 9.39 μM) and Ho-8910 (IC50 = 9.41 μM). Compound 5e exhibited IC50 value of 14.12 μM against A-549 and was more potent than other compounds in this series. Compound 5b induced the highest population of apoptotic cells (28.18 %) among the tested compounds at 10 μM. The results obtained from compounds 5 warrant their further optimization as new leads for developing new anticancer agents.
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This study was supported by the Self-innovation Project for Universities and Institutes of Jinan City (No. 201202035) and Program for Scientific Research Innovation Team in Colleges and Universities of Shandong Province (No. 21376125).