Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors
A new series of 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as tubulin polymerization inhibitors were synthesized and evaluated for the anti-proliferative activities. All newly prepared compounds were tested for their antiproliferative activity in vitro on the human breast cancer cell line (M...
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2022
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oai:doaj.org-article:2b24bd6be09e4de2baa6924943116c7d2021-11-04T04:27:46ZDesign, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors1878-535210.1016/j.arabjc.2021.103504https://doaj.org/article/2b24bd6be09e4de2baa6924943116c7d2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005190https://doaj.org/toc/1878-5352A new series of 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as tubulin polymerization inhibitors were synthesized and evaluated for the anti-proliferative activities. All newly prepared compounds were tested for their antiproliferative activity in vitro on the human breast cancer cell line (MCF-7) and human lung adenocarcinoma cell line (A549). Among them, compound 7b with a 4-methoxyl substituent at the phenylhydrazone moiety exhibited the most potent anticancer activity against MCF-7 and A549 with IC50 values of 1.77 ± 0.37 and 3.75 ± 0.11 μM, respectively. Interestingly, 7b displayed significant selectivity in inhibiting cancer cells over LO2 (normal human liver cells). Further mechanism studies revealed that 7b significantly arrested cell cycle at G2/M phase and induced apoptosis in a dose-dependent manner. Additionally, 7b effectively inhibited tubulin polymerization with an inhibitory manner similar to that of colchicine. Furthermore, molecular docking study suggested that 7b had high binding affinities for the colchicine binding pocket of tubulin. Hence, this study demonstrates for the first time that tetrahydroindole can be used as a functional group for the design and development of new tubulin polymerization inhibitors.Guangcheng WangMin HeWenjing LiuMeiyan FanYongjun LiZhiyun PengElsevierarticleTetrahydro-1H-indoleHydrazoneTubulin polymerization inhibitorsAnticancer activityChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103504- (2022) |
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DOAJ |
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DOAJ |
| language |
EN |
| topic |
Tetrahydro-1H-indole Hydrazone Tubulin polymerization inhibitors Anticancer activity Chemistry QD1-999 |
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Tetrahydro-1H-indole Hydrazone Tubulin polymerization inhibitors Anticancer activity Chemistry QD1-999 Guangcheng Wang Min He Wenjing Liu Meiyan Fan Yongjun Li Zhiyun Peng Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| description |
A new series of 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as tubulin polymerization inhibitors were synthesized and evaluated for the anti-proliferative activities. All newly prepared compounds were tested for their antiproliferative activity in vitro on the human breast cancer cell line (MCF-7) and human lung adenocarcinoma cell line (A549). Among them, compound 7b with a 4-methoxyl substituent at the phenylhydrazone moiety exhibited the most potent anticancer activity against MCF-7 and A549 with IC50 values of 1.77 ± 0.37 and 3.75 ± 0.11 μM, respectively. Interestingly, 7b displayed significant selectivity in inhibiting cancer cells over LO2 (normal human liver cells). Further mechanism studies revealed that 7b significantly arrested cell cycle at G2/M phase and induced apoptosis in a dose-dependent manner. Additionally, 7b effectively inhibited tubulin polymerization with an inhibitory manner similar to that of colchicine. Furthermore, molecular docking study suggested that 7b had high binding affinities for the colchicine binding pocket of tubulin. Hence, this study demonstrates for the first time that tetrahydroindole can be used as a functional group for the design and development of new tubulin polymerization inhibitors. |
| format |
article |
| author |
Guangcheng Wang Min He Wenjing Liu Meiyan Fan Yongjun Li Zhiyun Peng |
| author_facet |
Guangcheng Wang Min He Wenjing Liu Meiyan Fan Yongjun Li Zhiyun Peng |
| author_sort |
Guangcheng Wang |
| title |
Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| title_short |
Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| title_full |
Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| title_fullStr |
Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| title_full_unstemmed |
Design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| title_sort |
design, synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1h-indole derivatives as potential anticancer agents and tubulin polymerization inhibitors |
| publisher |
Elsevier |
| publishDate |
2022 |
| url |
https://doaj.org/article/2b24bd6be09e4de2baa6924943116c7d |
| work_keys_str_mv |
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