33821-71-5Relevant academic research and scientific papers
Harmine-based dual inhibitors targeting histone deacetylase (HDAC) and DNA as a promising strategy for cancer therapy
Lu, Dehua,Qu, Lailiang,Wang, Cheng,Luo, Heng,Li, Shang,Yin, Fucheng,Liu, Xingchen,Chen, Xinye,Luo, Zhongwen,Cui, Ningjie,Peng, Wan,Ji, Limei,Kong, Lingyi,Wang, Xiaobing
, (2022/01/20)
Overexpression of histone deacetylases (HDACs) are observed in different types of cancers, but histone deacetylase inhibitors (HDACIs) have not shown significant efficacy as monotherapy against solid tumors. Recently, studies demonstrated that it is promi
3-di-amine β- carboline base compound, preparation method and pharmaceutical composition and application thereof
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Paragraph 0145; 0169-0171; 0172, (2020/04/29)
The invention discloses a 3-position diamine connected beta-carboline alkali compound, and a preparation method, a medicinal composition and a use thereof. The above di-beta-carboline alkali compound and its medicinal salt are represented by general formu
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.
Cu-catalyzed mild and efficient oxidation of THβCs using air: Application in practical total syntheses of perlolyrine and flazin
Zheng, Bo,Trieu, Tien Ha,Meng, Tian-Zhuo,Lu, Xia,Dong, Jing,Zhang, Qiang,Shi, Xiao-Xin
, p. 6834 - 6839 (2018/02/23)
A mild, efficient and environmentally benign method for synthesis of aromatic β-carbolines via Cu(ii)-catalyzed oxidation of 1,2,3,4-tetrahydro-β-carbolines (THβCs) was developed, in which air (O2) was used as the clean oxidant. This method has advantages such as environmentally friendliness, mildness, very good tolerance of functional groups, high yielding and easy experiment operation. In addition, this new methodology was successfully applied in the efficient and practical total syntheses of β-carboline alkaloids perlolyrine and flazin.
Synthesis and preliminary evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors
Guo, Liang,Chen, Wei,Fan, Wenxi,Ma, Qin,Sun, Rongqin,Shao, Guang,Cao, Rihui
, p. 2177 - 2183 (2016/11/18)
A series of novel bivalent β-carbolines linked with an alkyl diamine spacer at the C-3 position were synthesized and evaluated as potent angiogenesis inhibitors. The results demonstrated that most bivalent β-carbolines displayed significant anti-proliferative effects against EA.HY926 human umbilical vein cell lines. Compound 8z was found to be the most potent anti-proliferative agent with an IC50 value of 1.10 μM against EA.HY926 cell lines. Preliminary investigations on the mechanisms of action revealed that compound 8z could dramatically inhibit EA.HY926 cell migration and tube formation in a dose-dependent manner. Moreover, compound 8z exhibited significant angiogenesis inhibitory effects in CAM assay, and the anti-angiogenic potency was comparable with that of the reference drug Endostar. These molecules might serve as candidates for further development into vascular-targeting antitumor drugs.
?-CARBOLINE, DIHYDRO-?-CARBOLINE AND TETRAHYDRO-?-CARBOLINE ALKALOID DERIVATIVES AND PREPARATION METHODS SAME AND USE IN ASPECTS OF PREVENTING AND TREATING PLANT VIRUSES, FUNGICIDES AND INSECTICIDES
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Paragraph 0174-0175, (2016/11/28)
The present invention relates to β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) and a method for preparing same and the use in the aspects of preventing and treating plant viruses, fungicides and insecticides. For the meaning of each group in formula (I) see the description. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives of the present invention show a particularly ourstanding anti-plant virus activity, and also have fungicidal and insecticidal activities.
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).
Synthesis and antiviral and fungicidal activity evaluation of β-carboline, dihydro-β-carboline, tetrahydro-β-carboline alkaloids, and their derivatives
Song, Hongjian,Liu, Yongxian,Liu, Yuxiu,Wang, Lizhong,Wang, Qingmin
, p. 1010 - 1018 (2014/03/21)
Six known β-carboline, dihydro-β-carboline, and tetrahydro-β-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 μg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 μg/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 μg/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 μg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibited good fungicidal activity against 14 kinds of fungi, especially compounds 4, 7, and 11.
Synthesis and antiviral and fungicidal activity evaluation of β-carboline, dihydro-β-carboline, tetrahydro-β-carboline alkaloids, and their derivatives
Song, Hongjian,Liu, Yongxian,Liu, Yuxiu,Wang, Lizhong,Wang, Qingmin
, p. 1010 - 1018 (2015/04/22)
Six known β-carboline, dihydro-β-carboline, and tetrahydro-β-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 μg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 μg/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 μg/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 μg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibited good fungicidal activity against 14 kinds of fungi, especially compounds 4, 7, and 11.
