Novel multi-target angiogenesis inhibitors as potential anticancer agents : Design, synthesis and preliminary activity evaluation
Copyright © 2024 Elsevier Inc. All rights reserved..
Based on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 μmol/L and 0.068 μmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Bioorganic chemistry - 145(2024) vom: 05. März, Seite 107211 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Qingqing [VerfasserIn] |
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| Links: |
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| Themen: |
ADMET prediction |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2024.107211 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368546179 |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Based on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 μmol/L and 0.068 μmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADMET prediction | |
| 650 | 4 | |a Angiogenesis inhibitors | |
| 650 | 4 | |a Anticancer agents | |
| 650 | 4 | |a Cytotoxicity | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
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| 700 | 1 | |a Zhang, Junyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanchen |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Jingkun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
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