449179-46-8Relevant articles and documents
Synthesis and anticancer activity of new coumarin-3-carboxylic acid derivatives as potential lactate transport inhibitors
Ji, Hong,Tan, Yaling,Gan, Nana,Zhang, Jing,Li, Shannuo,Zheng, Xuan,Wang, Zhaohua,Yi, Wei
, (2020/12/02)
As an oncometabolite, lactate plays a very important role in tumor proliferation, metastasis, angiogenesis, immune escape and other tumor biological functions. Pharmacological inhibition of lactate transport has been viewed as a promising therapeutic strategy to target a range of human cancers. In this study, a series of new coumarin-3-carboxylic acid derivatives 5a-t and 9a-b were synthesized and evaluated as lactate transport inhibitors. Their cytotoxic activity has been tested against three cell lines high-expressing and low-expressing monocarboxylate transporter 1 (MCT1) which acts as the main carrier for lactate. Compound 5c-e, 5g-i and 5m-o showed significant cytotoxicity and good selectivity against Hela and HCT116 cell lines with high MCT1 expression. Notably, coumarin-3-hydrazide 5o, the lead molecule with the most potent cytotoxic activity, exhibited significant anti-proliferation and apoptosis induction effects. Further studies revealed that compound 5o decreased the expression level of target MCT1, and suppressed the energetic metabolism of Hela and HCT116 cells by remarkably reducing glucose consumption and lactate production. Additionally, compound 5o induced intracellular lactate accumulation and inhibited lactate uptake, which implied that it blocked lactate transport via MCT1. These results indicate a good start point for the development of lactate transport inhibitors as new anticancer agents.
Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities
Cheng, Maojun,Ding, Jiaoli,Fang, Yuanying,Guan, Zhiyu,Guo, Jie,Jin, Yi,Liu, Jing,Wan, Yang,Wang, Rikang,Xie, Sai-Sai,Zhang, Zhipeng
, (2020/07/10)
A series of novel coumarin-based N-hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity a
Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents
Abdizadeh, Tooba,Kalani, Mohammad Reza,Abnous, Khalil,Tayarani-Najaran, Zahra,Khashyarmanesh, Bibi Zahra,Abdizadeh, Rahman,Ghodsi, Razieh,Hadizadeh, Farzin
, p. 42 - 62 (2017/03/24)
Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53–57.59?μM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50?=?0.80–14.81?μM) and HDAC1 inhibitory activity (IC50?=?0.47–0.87?μM and also, had no effect on Huvec (human normal cell line) viability (IC50?>?100?μM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47?±?0.02?μM near equal to the reference drug Entinostat (IC50?=?0.41?±?0.06?μM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.
