期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 26, 期 1, 页码 245-256出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.11.039
关键词
N-Methylpicolinamide; Thienopyrimidine; Pyridazinone; c-Met; Bioevaluation
资金
- National Natural Science Funds of China [21662014]
- Outstanding Youth Foundation of Jiangxi
- Natural Science Foundation of Jiangxi, China [20171BCB23078, 20171ACB21052, 20171BAB215073]
- Graduate Students' Science and Technology Innovation Project of Jiangxi Science & Technology Normal University [YC2016-X16]
- [GJJ160787]
Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were further evaluated for the activity against cMet, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Three compounds (35, 39 and 43) showed more active than positive control Foretinib against A549, HepG2 and MCF-7 cell lines. The most promising compound 43 showed superior activity against A549, HepG2 and MCF-7, with the IC50 values of 0.58 +/- 0.15 mM, 0.47 +/- 0.06 mM and 0.74 +/- 0.12 mM, which were 3.73-5.39-fold more activity than Foretinib, respectively. The experiments of enzyme-based showed that 43 restrain the c-Met selectively, with the IC50 values of 16 nM, which showed equal activity to Foretinib (14 nM) and better than the compound 5 (90 nM). Moreover, AO and Annexin V/PI staining and docking studies were carried out. (C) 2017 Elsevier Ltd. All rights reserved.
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