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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.
Journal of Medicinal Chemistry 2016 September 23
Cancer is the second cause of deaths worldwide and is forecasted to affect more that 22 million people in 2020. Despite dramatic improvement in its care over the last two decades, the treatment of resistant forms of cancer is still an unmet challenge. Thus, innovative and efficient treatments are still needed. In this context, we report herein the synthesis and the evaluation of a new class of bioactive molecules belonging to the N-(4-(3-aminophenyl(thiazol-2-yl)acetamide family. Structure-activity relationships could be driven and resulted in the discovery of lead compound 6b. The latter display high in vitro potency against both sensitive and resistant cancer cell lines on three models: melanoma, pancreatic cancer, and chronic myeloid leukemia (CML). 6b leads to cell death by concomitant induction of apoptosis and autophagy, shows good pharmacokinetic properties, and demonstrates a significant reduction of tumor growth in vivo on A375 xenograft model in mice.
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