Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

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...

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Main Authors:	Xiaofei Chen, Liang Guo, Qin Ma, Wei Chen, Wenxi Fan, Jie Zhang
Format:	Article
Language:	English
Published:	MDPI AG 2019-08-01
Series:	Molecules
Subjects:	asymmetric dimeric β-carboline acylhydrazone group cytotoxic antitumor structure–activity relationship
Online Access:	https://www.mdpi.com/1420-3049/24/16/2950

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spelling	doaj-8523c61287c045899d0e3b2d2fa811fc2020-11-24T21:32:33ZengMDPI AGMolecules1420-30492019-08-012416295010.3390/molecules24162950molecules24162950Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer AgentsXiaofei Chen0Liang Guo1Qin Ma2Wei Chen3Wenxi Fan4Jie Zhang5School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, ChinaSchool of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, ChinaXinjiang Huashidan Pharmaceutical Research Co. Ltd., 175 He Nan East Road, Urumqi 830011, ChinaXinjiang Huashidan Pharmaceutical Research Co. Ltd., 175 He Nan East Road, Urumqi 830011, ChinaXinjiang Huashidan Pharmaceutical Research Co. Ltd., 175 He Nan East Road, Urumqi 830011, ChinaSchool of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, ChinaUtilizing 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 <b>8z</b> showed antitumor activities with half-maximal inhibitory concentration (IC<sub>50</sub>) 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 <b>8z</b> on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound <b>8z</b> 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.https://www.mdpi.com/1420-3049/24/16/2950asymmetric dimeric β-carbolineacylhydrazone groupcytotoxicantitumorstructure–activity relationship
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Xiaofei Chen Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang
spellingShingle	Xiaofei Chen Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents Molecules asymmetric dimeric β-carboline acylhydrazone group cytotoxic antitumor structure–activity relationship
author_facet	Xiaofei Chen Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang
author_sort	Xiaofei Chen
title	Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
title_short	Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
title_full	Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
title_fullStr	Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
title_full_unstemmed	Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
title_sort	design, synthesis, and biological evaluation of novel n-acylhydrazone bond linked heterobivalent β-carbolines as potential anticancer agents
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-08-01
description	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 <b>8z</b> showed antitumor activities with half-maximal inhibitory concentration (IC<sub>50</sub>) 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 <b>8z</b> on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound <b>8z</b> 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.
topic	asymmetric dimeric β-carboline acylhydrazone group cytotoxic antitumor structure–activity relationship
url	https://www.mdpi.com/1420-3049/24/16/2950
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Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

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