54-59-1Relevant articles and documents
Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer
Liang, Ziyi,Lei, Fang,Deng, Jiedan,Zhang, Honghua,Wang, Yuqing,Li, Junfang,Shi, Tao,Yang, Xiaoyan,Wang, Zhen
, (2021/11/22)
Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.
Design, synthesis and bioactivity evaluation of novel N-phenyl-substituted evodiamine derivatives as potent anti-tumor agents
Hao, Xiangyong,Deng, Jiedan,Zhang, Honghua,Liang, Ziyi,Lei, Fang,Wang, Yuqing,Yang, Xiaoyan,Wang, Zhen
, (2022/01/10)
Natural products are important sources for the development of therapeutic medicine, among which evodia fruit has a wide range of medicinal properties in traditional Chinese medicine. Evodiamine, the main active component of evodia fruit, has various anti-cancer effects and has been proved to be a Topo inhibitor. From our previous attempts of modifying evodiamine, we found that the N14 phenyl substituted derivatives had showed great anti-tumor activity, which prompted us to further explore the novel structures and activities of these compounds. Compound 6f, as a N14 3-fluorinated phenyl substituted evodiamine derivative, showed a certain inhibitory activity against Topo I at 200 μM. By studying its anti-tumor effects in vitro, compound 6f could inhibit proliferation and induce apoptosis, as well as arrest the cell cycle of HGC-27 and HT-29 cell lines at G2/M phase in a concentration-dependent manner. Moreover, compound 6f could inhibit the migration and invasion of HGC-27 cell lines. Meanwhile, compound 6f could induce apoptosis of HGC-27 cells by inhibiting PI3K/AKT pathway. Overall, this work demonstrated that the N14 phenyl-substituted evodiamine derivatives had a good inhibitory effect on tumor cells in vitro, providing a promising strategy for developing potential anticancer agents for the treatment of gastrointestinal tumors.
Design, synthesis and biological evaluation of N-anthraniloyl tryptamine derivatives as pleiotropic molecules for the therapy of malignant glioma
Fan, Xiaohong,Li, Junfang,Long, Lin,Shi, Tao,Liu, Dan,Tan, Wen,Zhang, Honghua,Wu, Xiaoyan,Lei, Xiaoyong,Wang, Zhen
, (2021/06/09)
COX-2 and STAT3 are two key culprits in the glioma microenvironment. Herein, to inhibit COX-2 and block STAT3 signaling, we disclosed 27 N-anthraniloyl tryptamine compounds based on the combination of melatonin derivatives and N-substituted anthranilic acid derivatives. Among them, NP16 showed the best antiproliferative activity and moderate COX-2 inhibition. Of note, NP16 decreased the level of p-JAK2 and p-STAT3, and blocked the nuclear translocation of STAT3 in GBM cell lines. Moreover, NP16 downregulated the MMP-9 expression of BV2 cells in a co-culture system of BV2 and C6 glioma cells, abrogated the proliferative/invasive/migratory abilities of GBM cells, induced apoptosis by ROS and the Bcl-2-regulated apoptotic pathway, and induced obvious G2/M arrest in glioma cells in vitro. Furthermore, NP16 displayed favorable pharmacokinetic profiles covering long half-life (11.43 ± 0.43 h) and high blood-brain barrier permeability. Finally, NP16 effectively inhibited tumor growth, promoted the survival rate, increased the expression of E-cadherin and reduced overproduction of PGE2, MMP-9, VEGF-A and the level of p-STAT3 in tumor tissue, and improved the anxiety-like behavior in C6 glioma model. All these evidences demonstrated N-anthraniloyl tryptamine derivatives as multifunctional anti-glioma agents with high potency could drain the swamp to beat glioma.
Redox-neutral decarboxylative photocyclization of anthranilic acids
Huang, Huawen,Deng, Kun,Deng, Guo-Jun
supporting information, p. 8243 - 8247 (2020/12/29)
A mild metal-, catalyst-, and oxidant-free photoredox neutral system has been found to efficiently enable intramolecular decarboxylative cyclization of anthranilic acids. This facile protocol provides an alternative method for the synthesis of carbazoles. Mechanistic studies reveal a key photoinduced 6π-electrocyclization process and formic acid was released as the sole byproduct.
Light-Driven Intramolecular C?N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex
Jing, Dong,Lu, Cong,Chen, Zhuo,Jin, Songyang,Xie, Lijuan,Meng, Ziyi,Su, Zhishan,Zheng, Ke
supporting information, p. 14666 - 14672 (2019/09/06)
Reported herein is a visible-light-driven intramolecular C?N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.
Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents
Gao, Chunmei,Li, Bin,Zhang, Bin,Sun, Qinsheng,Li, Lulu,Li, Xi,Chen, Changjun,Tan, Chunyan,Liu, Hongxia,Jiang, Yuyang
supporting information, p. 1800 - 1807 (2015/03/30)
The discovery of new effective DNA-targeted antitumor agent is needed because of their clinical significance. As acridines can intercalate into DNA and benzimidazoles have the ability to bind in the DNA minor groove, a series of novel benzimidazole acridine derivatives were designed and synthesized to be new DNA-targeted compounds. MTT assay indicated that most of the synthesized compounds displayed good antiproliferative activity, among which compound 8l demonstrated the highest activity against both K562 and HepG-2 cells. Further experiments showed that 8l displayed good DNA-binding capability and inhibited topoisomerase I activity. Moreover, compound 8l could induce apoptosis in K562 cell lines through mitochondrial pathway. These data suggested that compound 8l might be potential as new DNA-binding and apoptosis-inducing antitumor agents.
Convenient access to substituted acridines by a Buchwald-Hartwig amination
Csuk, René,Barthel, Alexander,Raschke, Christian
, p. 5737 - 5750 (2007/10/03)
A convenient, high yield procedure for the synthesis of anthranilic acids carrying a variety of different substituents as well as their straightforward transformation into the corresponding 9-chloroacridines could be established by using modified Buchwald-Hartwig amination conditions.
