Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds

Wang, Jiabing; Yun, Di; Yao, Jiali; Fu, Weitao; Huang, Fei; Chen, Liping; Wei, Tao; Yu, Cuijuan; Xu, Haineng; Zhou, Xiaoou; Huang, Yanqing; Wu, Jianzhang; Qiu, Peihong; Li, Wulan

doi:10.1016/j.ejmech.2017.12.043

Cited by 50 publications

(17 citation statements)

References 38 publications

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“…Generally, preventing the growth of cancer cells by altering the regulation of cell cycle at a specific checkpoint is related with the various tumor developments (Wang et al 2018). Fu et al (2019) found that RFWD3 could stabilize p53 in response to DNA damage when the cell cycle checkpoint was activated, which showed RFWD3 may be associated with cell cycle arrest.…”

Section: Low Expression Of Rfwd3 Blocked Cell Cycle Progressionmentioning

confidence: 99%

Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Jia

Yang²,

Yan³

et al. 2020

gpb

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The E3 ligase RING finger and WD repeat domain 3 (RFWD3) can stabilize p53 in response to DNA damage, participate in replication checkpoint, and have an important role in multiple myeloma, testicular germ cell tumor and lung carcinogenesis. Its expression and molecular mechanisms have never been explored in gastric cancer. In present study, the RFWD3 was found over-expressed in the both AGS and HGC-27 gastric cancer cells. Knockdown of RFWD3 suppressed cells proliferation activity of gastric cancer cells. Further study showed that the down-regulation of RFWD3 promotes cell apoptosis, suppresses cell migration and invasion and blocks G2/M cell cycle progression, which may be related with AKT, ERK/P38 and Slug pathways. In summary, the results of the present study showed that RFWD3 might be an oncogene candidate for gastric cell proliferation and may have an important role in gastric carcinogenesis.

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Section: Low Expression Of Rfwd3 Blocked Cell Cycle Progressionmentioning

confidence: 99%

Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Jia

Yang²,

Yan³

et al. 2020

gpb

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“…The α,β-unsaturated ketone (Michael acceptor) pharmacophore, which was widely existent in numerous bioactive compounds, could form adducts with reactive thiol groups of proteins to induce modification and misfolding of protein, consequently resulting in a variety of pharmacological activities [ 16 ]. Especially, the incorporation of a Michael acceptor was believed to be capable of increasing anticancer activity [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway

Zhang

Song

et al. 2018

Molecules

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A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 μM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.

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“…The amide‐containing isatin–chalcone hybrids 51 (IC 50 : 3.2–14.1 μM, MTT assay) showed promising activity against BGC‐823, SGC‐7901, and NCI‐H460 cancer cell lines and the activity was superior to that of curcumin (IC 50 : 19.5–26.2 μM). [ 112 ] The representative hybrid 51a (IC 50 : 3.2–5.7 μM, MTT assay) displayed higher activity than the references curcumin (IC 50 : 19.5–26.2 μM) and xanthohumol (IC 50 : 6.9–10.0 μM) against BGC‐823, SGC‐7901, and NCI‐H460 cancer cell lines. Further study indicated that this hybrid exhibited a potent antigrowth and antimigration ability in a concentration‐dependent manner by arresting cells in the G2/M phase of the cell cycle.…”

Section: Isatin–coumarin Hybridsmentioning

confidence: 99%

Recent advances in isatin hybrids as potential anticancer agents

Ding

Zhou

Zeng

2020

Archiv der Pharmazie

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The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin‐based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin‐based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Thus, isatin‐based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin‐based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure–activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin‐based hybrids with high efficacy and low toxicity.

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Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds

Cited by 50 publications

References 38 publications

Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway

Recent advances in isatin hybrids as potential anticancer agents

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