- A Simple and straightforward synthesis of cinnamic acids and ylidene malononitriles via knoevenagel condensation employing dabco as catalyst
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An efficient method for the synthesis of substituted cinnamic acid and ylidene malanonitriles is developed via Knoevenagel condensation of aromatic aldehydes with malonic acid and malononitrile in the presence of catalytic amounts of DABCO. This method has many advantages, such as mild reaction conditions, excellent yields, short reaction times and no furthur purification required.
- Nagalakshmi,Diwakar,Govindh,Gopal Reddy,Venu,Bhargavi,Prasanna Devi,Murthy,Siddaiah
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p. 1561 - 1564
(2017/05/29)
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- Design, synthesis, and docking studies of afatinib analogs bearing cinnamamide moiety as potent EGFR inhibitors
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Two series of afatinib derivatives bearing cinnamamide moiety (10a-n and 11a-h) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, PC-3, MCF-7 and Hela). Two selected compounds (10e, 10k) were further evaluated for the inhibitory activity against EGFR and VEGFR2/KDR kinases. Seven of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Three of them are equal to more active than positive control afatinib against one or more cell lines. The most promising compound 10k showed the best activity against A549, PC-3, MCF-7 and Hela cancer cell lines and EGFR kinase, with the IC50 values of 0.07 ± 0.02 μM, 7.67 ± 0.97 μM, 4.65 ± 0.90 μM and 4.83 ± 1.28 μM, which were equal to more active than afatinib (0.05 ± 0.01 μM, 4.1 ± 2.47 μM, 5.83 ± 1.89 μM and 6.81 ± 1.77 μM), respectively. Activity of compounds 10e (IC50 9.1 nM) and 10k (IC50 3.6 nM) against EGFR kinase were equal to the reference compound afatinib (IC50 1.6 nM). Structure-activity relationships (SARs) and docking studies indicated that replacement of the aqueous solubility 4-(dimethylamino)but-2-enamide group by cinnamamide moiety didn't decrease the antitumor activity. The results suggested that methoxy substitution had a significant impact on the activity and methoxy substituted on C-4 or C-2,3,4 position was benefit for the activity.
- Tu, Yuanbiao,Ouyang, Yiqiang,Xu, Shan,Zhu, Yan,Li, Gen,Sun, Chao,Zheng, Pengwu,Zhu, Wufu
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p. 1495 - 1503
(2016/03/15)
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- Synthesis, biological evaluation and mechanism study of chalcone analogues as novel anti-cancer agents
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A series of novel chalcone analogues were designed, synthesized and evaluated as anticancer agents. The results of antiproliferative activity tests showed that most of the analogues exhibited moderate to very good antiproliferative activities with GI50 values in the micromol to sub-micromol range. Especially compound 10a gave 0.026 μM to 0.035 μM GI50 for five cancer cell lines. The mechanistic studies including tubulin polymerization inhibition, disruption of microtubule dynamics and cell cycle arrest assay demonstrated that compound 10a could effectively inhibit in vitro cellular tubulin polymerization, interfere with the mitosis, resulting in a prolonged G2/M cell cycle arrest and ultimately lead to cell apoptosis of cancer cells. Taken together, these results suggested that 10a may became a promising lead compound for development of new anticancer drugs.
- Chen, Jie,Yan, Jun,Hu, Jinhui,Pang, Yanqing,Huang, Ling,Li, Xingshu
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p. 68128 - 68135
(2015/08/24)
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- Synthesis, biological evaluation and mechanism study of a class of benzylideneindanone derivatives as novel anticancer agents
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A series of new benzylideneindanone derivatives were designed, synthesized and evaluated as antitumor agents. Structure-activity relationship (SAR) studies showed that derivatives with 4,5,6-trimethoxyl on an indanone moiety displayed good anti-proliferative activities. Especially, compound 5a demonstrated the most potent inhibitory activity, with GI50 values from 0.172 to 0.57 μM for five kinds of cancer cell lines. Further investigation showed that 5a could inhibit microtubule polymerization and thus induce G2/M phase arrest and apoptosis in A549 cells. Our findings revealed the benzylideneindanone moiety as a new attractive scaffold for mitosis-targeting drug discovery.
- Hu, Jinhui,Yan, Jun,Chen, Jie,Pang, Yanqing,Huang, Ling,Li, Xingshu
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p. 1318 - 1327
(2015/07/15)
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- Design and synthesis of novel 2-phenylaminopyrimidine (PAP) derivatives and their antiproliferative effects in human chronic myeloid leukemia cells
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A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2- ylamino)phenyl]acrylamide( 12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.
- Chang, Sheng,Yin, Shi-Liang,Wang, Jian,Jing, Yong-Kui,Dong, Jin-Hua
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experimental part
p. 4166 - 4179
(2009/12/28)
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