95202-52-1Relevant academic research and scientific papers
Molecular hybrid design, synthesis, in vitro and in vivo anticancer evaluation, and mechanism of action of N-acylhydrazone linked, heterobivalent β-carbolines
Chen, Wei,Chen, Xiaofei,Dai, Bin,Fan, Wenxi,Guo, Liang,Ma, Qin,Zhang, Jie
, (2020/02/05)
A series of N-acylhydrazone-linked, heterobivalent β-carboline derivatives was designed and synthesized from L-tryptophan in a nine-step reaction sequence. The effort resulted in the heterobivalent β-carbolines 10a–t in good yields. The target compounds were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). The in vitro cytotoxic activity of the synthesized compounds was evaluated against normal EA.HY926 cells and five cancer cell lines: LLC (Lewis lung carcinoma), BGC-823 (gastric carcinoma), CT-26 (murine colon carcinoma), Bel-7402 (liver carcinoma), and MCF-7 (breast carcinoma). Compound 10e, with an IC50 value of 2.41 μM against EA.HY926 cells, was the most potent inhibitor. It showed cytotoxicity against all five cancer cell lines of different origin – murine and human, with IC50 values ranging from 4.2 ± 0.7 to 18.5 ± 3.1 μM. A study of structure-activity relationships indicated that the influence on cytotoxic activities of the substituent in the R9′-position followed the tendency, 2,3,4,5,6-perfluorophenylmethyl > 4-fluorobenzyl > 3-phenylpropyl group. The antitumor efficacies of the selected compounds were also evaluated in mice. Compound 10e exhibited potent antitumor activity, with tumor inhibition of more than 40% for Sarcoma 180 and 36.7% for Lewis lung cancer. Furthermore, the pharmacological mechanisms showed that compound 10e has a certain impairment in the motility of LLC cells, which suggests the anti-metastatic potential. And compound 10e inhibited angiogenesis in chicken chorioallantoic membrane assay, and the anti-angiogenetic potency was more potent than the reference drug combretastatin A4-phosphate (CA4P) at a concentration 50 μM.
Design, synthesis, and biological evaluation of novel N-acylhydrazone bond linked heterobivalent β-carbolines as potential anticancer agents
Chen, Xiaofei,Guo, Liang,Ma, Qin,Chen, Wei,Fan, Wenxi,Zhang, Jie
, (2019/08/22)
Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 ± 0.9, 8.6 ± 1.4, 6.2 ± 2.5, 9.9 ± 0.5, and 5.7 ± 1.2 μM against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent β-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.
OBO-Protected Pyruvates as Reagents for the Synthesis of Functionalized Heteroaromatic Compounds
Alves Esteves, C. Henrique,Koyioni, Maria,Christensen, Kirsten E.,Smith, Peter D.,Donohoe, Timothy J.
supporting information, p. 4048 - 4051 (2018/07/15)
Pd-catalyzed α-arylation of methyl-OBO-ketone (OBO = 4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl) gives rise to arylated OBO-protected pyruvates. By appropriate prefunctionalization of the aryl ring or by subsequent functionalization at the α-carbonyl p
Synthesis and biological evaluation of novel 3,9-substituted β-carboline derivatives as anticancer agents
Chen, Yi-Fong,Lin, Yi-Chien,Chen, Jeng-Pang,Chan, Hsu-Chin,Hsu, Mei-Hua,Lin, Hui-Yi,Kuo, Sheng-Chu,Huang, Li-Jiau
, p. 3873 - 3877 (2015/08/24)
Abstract In our previous studies on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesised numerous substituted carbazole and α-carboline derivatives, which exhibited anticancer activity. In this study, we designed and synthesised a series of 3,9-substituted β-carbolines, by replacing the tricyclic rings of carbazole and α-carboline derivatives with isosteric β-carboline, and evaluated anticancer activity. We observed that 9-(2-methoxybenzyl)-β-carboline-3-carboxylic acid (11a) inhibited the growth of HL-60 cells by inducing apoptosis, with a half maximal inhibitory concentration of 4.0 μM. Our findings indicate that β-carboline derivatives can be used as lead compounds for developing novel antitumor agents.
Synthesis and biological evaluation of piperazine group-linked bivalent β-carbolines as potential antitumor agents
Sun, Rongqin,Liu, Rui,Zhou, Chi,Ren, Zhenghua,Guo, Liang,Ma, Qin,Fan, Wenxi,Qiu, Liqin,Yu, Huijuan,Shao, Guang,Cao, Rihui
, p. 2170 - 2174 (2015/12/11)
A series of novel bivalent β-carbolines with a piperazine group spacer between 3-methylene units were synthesized and evaluated as antitumor agents. The results demonstrated that compounds 7e and 7g exhibited the most potent cytotoxic activities against ten tumor cell lines. Structure-activity relationships analysis indicated that (1) the substituents in positions 1 and 9 of the β-carboline ring played a significant role in modulating the antitumor activity; (2) the introduction of alkyl groups into position-9 of the β-carboline nucleus enhanced their cytotoxic potencies and the butyl substituent was the optimal group. Investigation of the preliminary mechanism of action demonstrated that compound 7g showed obvious anti-angiogenic activity in the in vivo CAM assay, and the potency was similar to that of CA4P (200 μM).
The synthesis, structure and photoluminescent properties of solid-state green to yellow emitters based on β-carboline
Sun, Yi-Feng,Chen, Zhi-Yong,Liu, Ya-Ling,Li, Na,Li, Ji-Kun,Song, Hua-Can
, p. 512 - 522 (2013/01/13)
A series of solid-state green to yellow emitters based on β-carboline core were synthesized and characterized. The crystal structures of four of them were determined by single crystal X-ray diffraction analysis. The photoluminescent properties of β-carbol
HIV-integrase inhibitors, pharmaceutical compositions, and methods for their use
-
Page/Page column 20-21, (2008/06/13)
Beta-carboline hydroxamic acid compounds represented by formula (I) are described. The beta-carboline hydroxamic acid compounds and compositions containing those compounds may be used to inhibit or modulate the activity of HIV integrase enzyme and to trea
Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives
Cao, Rihui,Chen, Qi,Hou, Xuerui,Chen, Hongsheng,Guan, Huaji,Ma, Yan,Peng, Wenlie,Xu, Anlong
, p. 4613 - 4623 (2007/10/03)
A series of novel 9-substituted β-carboline derivatives was synthesized from the starting material harmine and l-tryptophan, respectively. Cytotoxic activities, acute toxicities, and antitumor effects of these compounds were investigated. A series of nove
Fused Indoles. Synthesis of β-Carbolines and Azerinoindoles from 3-(2-Alkylindol-3-yl)-2-azidoacrylates
Moody, Christopher J.,Ward, John G.
, p. 2895 - 2901 (2007/10/02)
Decomposition of the azidoacrylates (6) derived from 2-substituted indole-3-carbaldehydes gives pharmacologically important β-carbolines , azepinoindoles (13), or enamines (14) depending on the conditions.The formation of azepinoindoles, shown to proceed by cyclisation of the initially formed enamines, represents a new reaction of vinyl azides which is particularly favoured in the indole series.
