Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good ac...

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Main Authors:	Ling Zhang, Yunlong Song, Jingjing Huang, Jia Liu, Wenwen Zhu, Youjun Zhou, Jiaguo Lv, Canhui Zheng, Ju Zhu
Format:	Article
Language:	English
Published:	MDPI AG 2015-05-01
Series:	International Journal of Molecular Sciences
Subjects:	1,4-disubstituted-3,4-dihydroisoquinoline tubulin polymerization inhibitor antitumor agent
Online Access:	http://www.mdpi.com/1422-0067/16/5/10173

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spelling	doaj-0597fa695e434544b0c43c7538516fc92020-11-24T21:14:26ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-05-01165101731018410.3390/ijms160510173ijms160510173Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization InhibitorsLing Zhang0Yunlong Song1Jingjing Huang2Jia Liu3Wenwen Zhu4Youjun Zhou5Jiaguo Lv6Canhui Zheng7Ju Zhu8School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaSchool of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaA series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.http://www.mdpi.com/1422-0067/16/5/101731,4-disubstituted-3,4-dihydroisoquinolinetubulin polymerization inhibitorantitumor agent
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ling Zhang Yunlong Song Jingjing Huang Jia Liu Wenwen Zhu Youjun Zhou Jiaguo Lv Canhui Zheng Ju Zhu
spellingShingle	Ling Zhang Yunlong Song Jingjing Huang Jia Liu Wenwen Zhu Youjun Zhou Jiaguo Lv Canhui Zheng Ju Zhu Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors International Journal of Molecular Sciences 1,4-disubstituted-3,4-dihydroisoquinoline tubulin polymerization inhibitor antitumor agent
author_facet	Ling Zhang Yunlong Song Jingjing Huang Jia Liu Wenwen Zhu Youjun Zhou Jiaguo Lv Canhui Zheng Ju Zhu
author_sort	Ling Zhang
title	Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
title_short	Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
title_full	Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
title_fullStr	Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
title_full_unstemmed	Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
title_sort	design, synthesis and biological evaluation of 1,4-disubstituted-3,4-dihydroisoquinoline compounds as new tubulin polymerization inhibitors
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1422-0067
publishDate	2015-05-01
description	A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.
topic	1,4-disubstituted-3,4-dihydroisoquinoline tubulin polymerization inhibitor antitumor agent
url	http://www.mdpi.com/1422-0067/16/5/10173
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Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

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