Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells
Abstract 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 (...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Chemistry |
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| Online Access: | https://doi.org/10.1186/s13065-023-01102-1 |
| _version_ | 1797377192718499840 |
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| author | Jixiang Gao Jinyi Liu Tao Yu Chenggong Xu Hao Sun Chunbo Lu Wenjia Dan Jiangkun Dai |
| author_facet | Jixiang Gao Jinyi Liu Tao Yu Chenggong Xu Hao Sun Chunbo Lu Wenjia Dan Jiangkun Dai |
| author_sort | Jixiang Gao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T19:49:15Z |
| format | Article |
| id | doaj.art-4f70cdb50d4641f4875696805203833e |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-03-08T19:49:15Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-4f70cdb50d4641f4875696805203833e2023-12-24T12:08:59ZengBMCBMC Chemistry2661-801X2023-12-0117111210.1186/s13065-023-01102-1Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cellsJixiang Gao0Jinyi Liu1Tao Yu2Chenggong Xu3Hao Sun4Chunbo Lu5Wenjia Dan6Jiangkun Dai7School of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversitySchool of Life Science and Technology, Weifang Medical UniversityAbstract 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.https://doi.org/10.1186/s13065-023-01102-1Eudistomin USynthesisAnti-melanomaTranscriptomeDNA |
| spellingShingle | Jixiang Gao Jinyi Liu Tao Yu Chenggong Xu Hao Sun Chunbo Lu Wenjia Dan Jiangkun Dai Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells BMC Chemistry Eudistomin U Synthesis Anti-melanoma Transcriptome DNA |
| title | Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells |
| title_full | Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells |
| title_fullStr | Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells |
| title_full_unstemmed | Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells |
| title_short | Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells |
| title_sort | synthesis of 3 formyl eudistomin u with anti proliferation anti migration and apoptosis promoting activities on melanoma cells |
| topic | Eudistomin U Synthesis Anti-melanoma Transcriptome DNA |
| url | https://doi.org/10.1186/s13065-023-01102-1 |
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