MOLECULAR DIVERSITY
·
2024
·
IF 3.9
Xie Tianyu,Hu Wenbo,You Lin,Wang Xin
With cabozantinib as the precursor, a novel small molecule inhibitors of c-Met kinase with thieno [2,3- b ] pyridine as the scaffold were designed, synthesized and evaluated for their biological activity against A549, Hela and MCF-7 cell lines. The in vitro activities of 16 compounds were tested by MTT method with cabozantinib as control drug. Most compounds had moderate to strong inhibitory activities on cells. Among them, compound 10 had the strongest inhibitory activity, which was superior to the lead compound cabozantinib. Its IC 50 values for A549, Hela and MCF-7 cells were 0.005, 2.833 and 13.581 μM, respectively. The colony formation assay demonstrated that compound 10 significantly inhibited the colony formation of A549 cells and suppressed their growth in a concentration-dependent manner. The wound healing assay showed that compound 10 could effectively inhibit the migration of cancer cells compared to a blank control group. The AO/EB assay demonstrated that compound 10 possesses the capability to effectively trigger apoptosis in a concentration-dependent manner. The elementary structure–activity relationship, molecular docking and pharmacokinetics studies revealed the significance of thieno [2,3- b ] pyridine derivatives in anti-tumor activity. Graphical abstract
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 7
·3760-3767
·
IF 3.108
Lianbao Ye,Jie Wu,Weiqiang Chen,Yu Feng,Zhibing Shen
Germacrone is a major activity component found in Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria. In the present study, novel germacrone derivatives were first designed based on the theories of bioalkylating agents, synthesized, and then investigated for their inhibition effects on Bel-7402, HepG2, A549, and HeLa cells. Moreover, the study also evaluated the inhibition of these derivatives on c-Met kinase, which is expressed in a number of cancers. The results indicated that most of the compounds showed a stronger inhibitory effect on cancer cells and c-Met kinase than germacrone. Besides these findings, molecular docking studies were also carried out to analyze the results and explain the molecular mechanism of activities to c-Met kinase. Molecular dynamics simulations have been carried out for the further evaluation of binding stabilities between the compounds and their receptors.
研究领域:
药理学
·
肿瘤学
·
计算生物学
✓ 已验证
DOI
高影响因子
Oncotarget
·
2017
·
IF 5.168
Jie Wu,Yu Feng,Chao Han,Wu Huang,Zhibin Shen,Mengdie Yang,Weiqiang Chen,Lianbao Ye
Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary . The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.
研究领域:
药理学
·
有机化学
·
计算生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2022
·
IF 1.573
Wen Zhao,Ye Xu,Qingkui Guo,Wenliang Qian,Chen Zhu,Min Zheng
ObjectiveTo synthesize a novel chalcone-1,3,4-thiadiazole hybrid and investigate its anticancer effects against NCI-H460 cells.Methods(E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, 1,3-dibromopropane and 1,3,4-thiadiazole-2-thiol were used as chemical materials to synthesize compound ZW97. The NCI-H460 lung cancer cell line was selected to explore the antitumor effects of compound ZW97 in vitro and in vivo.ResultsCompound ZW97 selectively inhibited cell proliferation against lung cancer cell lines NCI-H460, HCC-44 and NCI-H3122 with IC50 values of 0.15 μM, 2.06 μM and 1.17 μM, respectively. ZW97 suppressed migration and the epithelial–mesenchymal transition process in NCI-H460 cells in a concentration-dependent manner. Based on the kinase activity results and docking analysis, compound ZW97 is a novel tyrosine-protein kinase Met (c-Met kinase) inhibitor. It also inhibited NCI-H460 cell growth in xenograft models without obvious toxicity to normal tissues.ConclusionsCompound ZW97 is a potential c-Met inhibitor that might be a promising agent to treat lung cancer by inhibiting the epithelial–mesenchymal transition process.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）