- Discovery of novel dual c-Met/HDAC inhibitors as a promising strategy for cancer therapy
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Owing to the low efficacy and acquired resistance in clinical trials of c-Met inhibitors, based on the synergistic effects between c-Met and HDAC, novel c-Met and HDAC dual inhibitors were designed and synthesized. We introduced 2-pyrrolidinone to form the 5-atoms linker for c-Met inhibitor and hydroxamic acid as a zinc binding motif for HDAC inhibitor. The highly active dual inhibitor 15f showed excellent and balanced activity against both c-Met (IC50 = 12.50 nM) and HDAC1 (IC50 = 26.97 nM). In those tested tumor cell lines, 15f exhibits efficient antiproliferative activity with greater potency than Vorinostat (SAHA) and Cabozantinib (XL184). However, by comparing with an equimolar mixture of SAHA and Foretinib, we did not observe the compounds showed clearly synergistic antiproliferative effect. Nevertheless, compound 15f was found to induce apoptosis and cause cell cycle arrest in G2/M phase. This proof-of-concept study provides an efficient strategy for discovery of multitarget antitumor drugs.
- Chen, Fei,Dong, Yuhong,Gong, Ping,Hu, Hao,Liu, Yajing
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- Sodium borohydride-iodine mediated reduction of γ-lactam carboxylic acids followed by DDQ mediated oxidative aromatisation: a simple approach towards N-aryl-formylpyrroles and 1,3-diaryl-formylpyrroles
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A simple methodology for the conversion of substituted N-aryl-γ-lactam 2/3-carboxylic acids to substituted N-aryl-2/3-formyl-pyrroles has been developed. Several N-aryl-γ-lactam 2/3-carboxylic acids were reduced to substituted (N-aryl-pyrroliden-2/3-yl)-m
- Haldar, Pranab,Barman, Gopa,Ray, Jayanta K.
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p. 3049 - 3056
(2007/10/03)
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- Method for production of pyrrolidinone derivatives
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A compound represented by the following formula (12) useful as an intermediate for production of drug or agricultural chemical: (wherein R21to R25are each independently a hydrogen atom, a hydroxyl group, a halogen atom, an alkyl grou
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