- Design, synthesis, and biological evaluation of novel N-acylhydrazone bond linked heterobivalent β-carbolines as potential anticancer agents
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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.
- Chen, Xiaofei,Guo, Liang,Ma, Qin,Chen, Wei,Fan, Wenxi,Zhang, Jie
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- Synthesis and biological evaluation of piperazine group-linked bivalent β-carbolines as potential antitumor agents
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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).
- Sun, Rongqin,Liu, Rui,Zhou, Chi,Ren, Zhenghua,Guo, Liang,Ma, Qin,Fan, Wenxi,Qiu, Liqin,Yu, Huijuan,Shao, Guang,Cao, Rihui
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supporting information
p. 2170 - 2174
(2015/12/11)
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- Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives
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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
- Cao, Rihui,Chen, Qi,Hou, Xuerui,Chen, Hongsheng,Guan, Huaji,Ma, Yan,Peng, Wenlie,Xu, Anlong
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p. 4613 - 4623
(2007/10/03)
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