AI Article Synopsis
- A series of novel N-acyclic uracil analogs were synthesized and tested against malignant tumor cell lines using advanced palladium catalyzed techniques.
- The C-5-Furan-2-yl uracil derivative showed stronger potency against breast cancer cells than the standard treatment, 5-fluorouracil, while other alkynyl derivatives had similar effectiveness.
- These compounds induced cell death primarily through apoptosis and influenced sphingolipid signaling by altering the expression of acid ceramidase, highlighting their potential for targeted breast cancer therapy.
Article Abstract
A series of novel N-acyclic uracil analogs with linear, branched, aromatic, and cyclopropyl-alkynyl as well as heteroaryl moieties at C-5 were prepared using palladium catalyzed Sonogashira and Stille cross-coupling and evaluated against malignant tumor cell lines. C-5-Furan-2-yl uracil derivative 6 was shown to be more potent against MCF-7 than the reference drug 5-fluorouracil (5-FU), while C-5-alkynyl uracil derivatives 9c and 9e exhibited antibreast cancer activities comparable to 5-FU. Selected compounds induced cell death, partially due to apoptosis, of MCF-7 breast cancer cells. Abrogation of acid ceramidase (ASAH1) expression of 9c and 9e indicated that these compounds could perturb ASAH1-mediated sphingolipid signaling. The selective activity of 9c and 9e against breast cancer cells via the ASAH1-mediated signaling, as a molecular target, might have a great advantage for potential future therapeutic use.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645252 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.5b00298 | DOI Listing |
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