72502-82-0Relevant academic research and scientific papers
Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3
Ma, Shumeng,Zhu, Longqing,Fan, Xiaohong,Luo, Tian,Liu, Dan,Liang, Ziyi,Hu, Xiaoling,Shi, Tao,Tan, Wen,Wang, Zhen
, (2020/12/02)
The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of “scissors” cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 μM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.
Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma
Fan, Xiaohong,Deng, Jiedan,Shi, Tao,Wen, Huaixiu,Li, Junfang,Liang, Ziyi,Lei, Fang,Liu, Dan,Zhang, Honghua,Liang, Yan,Hao, Xiangyong,Wang, Zhen
, (2021/07/14)
Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-β/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.
Palladium-Catalyzed Multistep Tandem Carbonylation/N-Dealkylation/Carbonylation Reaction: Access to Isatoic Anhydrides
Wang, Shoucai,Li, Xuan,Zang, Jiawang,Liu, Meichen,Zhang, Siyu,Jiang, Guangbin,Ji, Fanghua
, p. 2672 - 2679 (2020/02/04)
A novel and efficient synthesis of isatoic anhydride derivatives was developed via palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation reaction with alkyl as the leaving group and tertiary anilines as nitrogen nucleophiles. This approach features good functional group compatibility and readily available starting materials. Furthermore, it provided a convenient approach for the synthesis of biologically and medicinally useful evodiamine.
Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation
Deng, Xuemei,Fan, Xiaohong,Feng, Yiyue,Li, Junfang,Lu, Yingmei,Ma, Shumeng,Shi, Tao,Tan, Wen,Wang, Zhen,Wen, Huaixiu,Zhao, Quanyi
, (2020/03/17)
Because of the complex etiology in neuroinflammatory process, the design of multifunctional agents is a potent strategy to cure neuroinflammatory diseases including AD and PD. Herein, based on the combination principles, 23 of N-salicyloyl tryptamine deri
METHOD FOR PRODUCING EVODIAMINE
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Paragraph 0032-0034; 0041, (2019/08/26)
PROBLEM TO BE SOLVED: To provide a method for efficiently producing evodiamine. SOLUTION: A method for producing evodiamine of formula (1) includes the steps of: reacting a compound of the formula (2) and orthoformic ester in the presence of a non-reducti
A concise synthesis and biological study of evodiamine and its analogues
Deng, Jie-Dan,Lei, Shuai,Jiang, Yi,Zhang, Hong-Hua,Hu, Xiao-Ling,Wen, Huai-Xiu,Tan, Wen,Wang, Zhen
supporting information, p. 3089 - 3092 (2019/03/29)
Efficient access to evodiamine and its analogues is presented via Lewis acid catalysis. In this reaction, three chemical bonds and two heterocyclic-fused rings are constructed in one step. The reaction shows good functional group tolerance and atom economy, and various heteroatom-containing evodiamine analogues are obtained in moderate to excellent yields even on a gram scale. An anti-tumor study in vitro demonstrates compound 2b possesses potent efficacy against hepatoma cell line (IC50 = 5.7 μM).
A method for utilizing the carbonylation reaction three-step synthetic evodiamine method (by machine translation)
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Paragraph 0013; 0020; 0023, (2018/04/02)
The invention discloses a three-step synthesis of carbonylation reaction evodiamine method. First of all in order to N, N - dimethyl aniline as the raw materials of reaction by oxidative carbonylation reaction to obtain N - methyl isatin anhydride, by ammonolysis reaction to obtain N - (2 - indole ethyl) - 2 - (methylamino) benzamide, finally through the cyclization reaction of the three-step synthesis tetradium alkalizing compound. The method of the invention the synthesis of novel means, reaction and is simple, the synthesis step is succinct, mild reaction conditions, the process is simple, consistent with the requirements of the development of green chemistry, and utilize the carbonylation reaction has succeeded in synthesizing evodiamine. (by machine translation)
One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
Wang, Zi-Xuan,Xiang, Jia-Chen,Wang, Miao,Ma, Jin-Tian,Wu, Yan-Dong,Wu, An-Xin
supporting information, p. 6380 - 6383 (2018/10/20)
The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation.
Studies of Rutaecarpine and Related Quinazolinocarboline Alkaloids
Bergman, Jan,Bergman, Solveig
, p. 1246 - 1255 (2007/10/02)
Quinazolinocarboline alkaloids, e.g., rutaecarpine (1), can readily be synthesized by treating tryptamine with 2-(trifluoromethyl)-4H-3,1-benzoxazin-4-one (quickly generated in situ from trifluoroacetic anhydride (TFAA) and 2H-3,1-benzoxazine-2,4(1H)-dione.The product formed, 3--2-(trifluoromethyl)-4-(3H)-quinazolinone (5), is then cyclized (HCl/HOAc) to 13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine (6), whereupon CF3H is eliminated by treatment with base.The sequence can conveniently be performed as a three-reaction one-pot procedure giving rutaecarpine (1) in 99percent yield within 3h.The approach can readily be extended to the synthesis of evodiamine (2), 13,13b-dehydroevodiamine (38a), and 13b,14-dihydrorutaecarpine (21).Thus treatment of 3--4(3H)-quinazolinone (19) with TFAA affected cyclization to 13b-(trifluoroacetyl)-13b,14-dihydrorutaecarpine (20), which can be readily hydrolyzed to 13b,14-dihydrorutaecarpine (21).
