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Design, synthesis, and antitumor activity evaluation of pretubulysin analogs. | LitMetric
Pretubulysin, a biosynthetic precursor of the tubulysins, shows potent biological activity in a variety of tumor cell lines. Although there are several total synthesis routes to tubulysin and pretubulysin reported, the commercialization still has been hampered due to the complexity of the structure. To find structurally simpler pretubulysin analogs, a series of 2-(3-(methylamino)propyl)thiazole-4-carboxamides are designed and synthesized, and their anticancer activities are screened using MCF-7 (breast cancer), and NCI-H157 (lung cancer) cell lines. Taxol (IC = 0.01 µM) and pretubulysin are used as the control. Compounds 8c (IC = 0.05 µM, MCF-7; 0.09 µM, NCI-H157) and 8h (IC = 0.01 µM, MCF-7; 0.02 µM, NCI-H157) exhibited certain antitumor activities comparable to those of Taxol. The urea analogs of pretubulysin might represent a promising scaffold for the further development of novel antitumor drugs.
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