Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells
© 2023. The Author(s)..
The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC50 = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico. Colony formation and cell cycle arrest assays revealed that EU-5 suppressed cell proliferation by causing cell cycle arrest at G0/G1 phase. Wound healing and transwell assays suggested that EU-5 could effectively inhibit migration of A375 cells in a dose-dependent manner. Calcein-AM/PI staining, Annexin V-FITC/PI apoptosis detection, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), transcriptomics, quantitative real‑time polymerase chain reaction (qRT‑PCR), spectrometric titration and molecular docking assays indicated that EU-5 could activate p53 signaling pathway and trigger mitochondria-mediated cell apoptosis. Taken together, this study provided a promising lead structure for the design of a new generation of anti-melanoma drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
BMC chemistry - 17(2023), 1 vom: 20. Dez., Seite 184 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Jixiang [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-melanoma |
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| Anmerkungen: |
Date Revised 23.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s13065-023-01102-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366148214 |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC50 = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico. Colony formation and cell cycle arrest assays revealed that EU-5 suppressed cell proliferation by causing cell cycle arrest at G0/G1 phase. Wound healing and transwell assays suggested that EU-5 could effectively inhibit migration of A375 cells in a dose-dependent manner. Calcein-AM/PI staining, Annexin V-FITC/PI apoptosis detection, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), transcriptomics, quantitative real‑time polymerase chain reaction (qRT‑PCR), spectrometric titration and molecular docking assays indicated that EU-5 could activate p53 signaling pathway and trigger mitochondria-mediated cell apoptosis. Taken together, this study provided a promising lead structure for the design of a new generation of anti-melanoma drugs | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a DNA | |
| 650 | 4 | |a Eudistomin U | |
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| 650 | 4 | |a Transcriptome | |
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| 700 | 1 | |a Yu, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Chenggong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chunbo |e verfasserin |4 aut | |
| 700 | 1 | |a Dan, Wenjia |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jiangkun |e verfasserin |4 aut | |
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