Abstract:
BACKGROUND:The genetic heterogeneity of tumor cells and the development of therapy-resistant cancer cells in addition to the high cost necessitate the continuous development of novel targeted therapies. METHODS:In this regard, 14 novel benzoxazinone derivatives were synthesized and examined for anticancer activity against two human epithelial cancer cell lines; breast MCF-7 and liver HepG2 cells. 6,8-Dibromo-2- ethyl-4H-benzo[d][1,3]oxazin-4-one was subjected to react with nitrogen nucleophiles to afford quinazolinone derivatives and other related moieties (3-12). Benzoxazinone 2 responds to attack with oxygen nucleophile such as ethanol to give ethyl benzoate derivative 13. The reaction of benzoxazinone 2 with carbon electrophile such as benzaldehyde derivatives afforded benzoxazinone derivatives 14a and 14b.The structure of the prepared compounds was confirmed with spectroscopic tools including IR, 1H-NMR, and 13C-NMR. RESULTS:Derivatives 3, 9, 12, 13, and 14b exhibited high antiproliferative activity and were selective against cancer cells showing no toxicity in normal fibroblasts. Derivative 3 with NH-CO group in quinazolinone ring was effective only against breast cells, while derivative 12 with NH-CO group in imidazole moiety was only effective against liver cells probably through arresting cell cycle and enabling repair mechanisms. The other derivatives (9, 13, and 14b) had broader antiproliferative activity against both cell lines. These derivatives enhance the expression of the p53 and caspases 9 and 3 to varying degrees in both cell lines. Derivative 14b caused the highest induction in the investigated genes and was the only derivative to inhibit the EGFR activity. CONCLUSIONS:The unique features about derivative 14b could be attributed to its high lipophilicity, high carbon content, or its extended conjugation through planar aromatic system. More investigations are required to identify the lead compound(s) in animal models.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
El-Hashash MA,Ali AT,Hussein RA,El-Sayed WMdoi
10.2174/1871520619666190201145221subject
Has Abstractpub_date
2019-01-01 00:00:00pages
538-545issue
4eissn
1871-5206issn
1875-5992pii
ACAMC-EPUB-96306journal_volume
19pub_type
杂志文章abstract::Epigenetic modifications can affect numerous mechanisms used by neoplastic cells to evade immune control. In melanoma epigenetic defects, caused by dysregulations in the expression of genome writers, erasers, or readers, play a significant role in the reduced expression of molecules required for efficient immune recog...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520616666160425110401
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abstract:BACKGROUND:Lung cancer is one of the most prevalent malignancies and thus the development of novel therapeutic agents for managing lung cancer is imperative. Tetrandrine, a bis-benzyltetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, has been found to exert cytotoxic effects on cancerous cells....
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520615666150617111414
更新日期:2016-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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abstract::Chronic lymphocytic leukemia (CLL) is the most frequent type of hematological cancer in the Western World. An accumulation of leukemic cells in peripheral blood of patients is a result of apoptosis disturbances as well as an increase in germinal centers CLL cell proliferation. The differences between CLL patients in t...
journal_title:Anti-cancer agents in medicinal chemistry
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abstract:BACKGROUND:Human P-glycoprotein (P-gp) is a transmembrane protein that belongs to the ATPBinding Cassette (ABC) transporters family. Physiologically, it exports toxins out of the cell, however, its overexpression leads to the phenomena of Multidrug-Resistance (MDR) by exporting a diverse range of compounds, which are s...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2017-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2017-01-01 00:00:00
abstract::The epidermal growth factor receptor (EGFR) is dysregulated in various tumour types such as glioblastoma multiforme (GBM), breast cancer, ovarian carcinoma, non-small cell lung cancer and other cancers. As the intracellular tyrosine kinase of the EGFR activates signalling cascades leading to cell proliferation, angiog...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2010-05-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2017-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666151009114759
更新日期:2016-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2019-01-01 00:00:00