Design, synthesis, and biological evaluation of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives as anticancer agents
Abstract A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells ($ IC_{50} $ = 0.37, 0.73 and 0.95 µM, respectively) which were significantly more potent than sorafenib as the reference drug ($ IC_{50} $ = 7.91 µM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2..
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Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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Enthalten in: |
Medicinal chemistry research - 29(2020), 11 vom: 24. Aug., Seite 2000-2010 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Aghcheli, Ayoub [VerfasserIn] |
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Links: |
Volltext [lizenzpflichtig] |
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Themen: |
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Anmerkungen: |
© Springer Science+Business Media, LLC, part of Springer Nature 2020 |
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doi: |
10.1007/s00044-020-02616-2 |
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funding: |
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PPN (Katalog-ID): |
OLC211948161X |
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520 | |a Abstract A novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a–l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d, 5g, and 5k) showed promising activities, especially against Hela cancer cells ($ IC_{50} $ = 0.37, 0.73 and 0.95 µM, respectively) which were significantly more potent than sorafenib as the reference drug ($ IC_{50} $ = 7.91 µM). Flow cytometry analysis revealed that the prototype compounds (5d, 5g, and 5k) significantly induced apoptotic cell death in HeLa cancer cells and blocked the cell cycle at the sub-G1 phase. Moreover, in silico docking study confirmed the binding of the prototype compound to the active site of VEGFR-2. | ||
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