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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Marine drugs
2024
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39728112/ |
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| _version_ | 1868266263042588673 |
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| author | Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue |
| author_facet | Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue |
| collection | PubMed - marine biology |
| contents | Structure-Activity Relationship Study of Majusculamide D: Overcoming Metabolic Instability and Severe Toxicity with a Fluoro Analogue. Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue Animals Humans Mice Structure-Activity Relationship Antineoplastic Agents Cell Line, Tumor Cyanobacteria Cell Proliferation Xenograft Model Antitumor Assays Pancreatic Neoplasms Aquatic Organisms Oligopeptides Cell Movement Majusculamide D, isolated from the marine cyanobacterium , is an anticancer lipopentapeptide consisting of fatty acid, tripeptide, and pyrrolyl proline moieties. In this work, by utilizing a convergent synthetic approach, late-stage modification, and bioisostere strategy, 26 majusculamide D analogues were synthesized, and two ( and ) demonstrated IC values < 1 nM against PANC-1 cancer cells. The results summarized a preliminary structure-activity relationship mainly at the C23, C4, C34, and C10 sites. A series of in vitro assays, including wound healing, transwell, clone formation, EdU, and western blot, confirmed that majusculamide D inhibited the migration, invasion, and proliferation of pancreatic cancer cells. The optimized fluorinated analogue demonstrated a notable enhancement in stability during the mouse plasma assay (>50% left after 24 h), exhibited tumor-suppressive effects (51.5% at a dosage of 5 mg/kg), and successfully mitigated the severe toxicity (no mouse dead) observed in the group treated with majusculamide D (3 mice dead) in a xenografted mouse model. |
| format | Artículo científico |
| id | pubmed_39728112 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Marine drugs |
| record_format | pubmed |
| spellingShingle | Structure-Activity Relationship Study of Majusculamide D: Overcoming Metabolic Instability and Severe Toxicity with a Fluoro Analogue. Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue Animals Humans Mice Structure-Activity Relationship Antineoplastic Agents Cell Line, Tumor Cyanobacteria Cell Proliferation Xenograft Model Antitumor Assays Pancreatic Neoplasms Aquatic Organisms Oligopeptides Cell Movement Structure-Activity Relationship Study of Majusculamide D: Overcoming Metabolic Instability and Severe Toxicity with a Fluoro Analogue. Zhao, Xiuhe Xi, Xiaonan Zhang, Mingxiao Lv, Mengxue Zhang, Xiang Lu, Yaxin Wang, Liang Chen, Yue Animals Humans Mice Structure-Activity Relationship Antineoplastic Agents Cell Line, Tumor Cyanobacteria Cell Proliferation Xenograft Model Antitumor Assays Pancreatic Neoplasms Aquatic Organisms Oligopeptides Cell Movement Majusculamide D, isolated from the marine cyanobacterium , is an anticancer lipopentapeptide consisting of fatty acid, tripeptide, and pyrrolyl proline moieties. In this work, by utilizing a convergent synthetic approach, late-stage modification, and bioisostere strategy, 26 majusculamide D analogues were synthesized, and two ( and ) demonstrated IC values < 1 nM against PANC-1 cancer cells. The results summarized a preliminary structure-activity relationship mainly at the C23, C4, C34, and C10 sites. A series of in vitro assays, including wound healing, transwell, clone formation, EdU, and western blot, confirmed that majusculamide D inhibited the migration, invasion, and proliferation of pancreatic cancer cells. The optimized fluorinated analogue demonstrated a notable enhancement in stability during the mouse plasma assay (>50% left after 24 h), exhibited tumor-suppressive effects (51.5% at a dosage of 5 mg/kg), and successfully mitigated the severe toxicity (no mouse dead) observed in the group treated with majusculamide D (3 mice dead) in a xenografted mouse model. |
| title | Structure-Activity Relationship Study of Majusculamide D: Overcoming Metabolic Instability and Severe Toxicity with a Fluoro Analogue. |
| topic | Animals Humans Mice Structure-Activity Relationship Antineoplastic Agents Cell Line, Tumor Cyanobacteria Cell Proliferation Xenograft Model Antitumor Assays Pancreatic Neoplasms Aquatic Organisms Oligopeptides Cell Movement |
| url | https://pubmed.ncbi.nlm.nih.gov/39728112/ |