Meščić, Andrijana Harej, Anja Klobučar, Marko Glavač, Danijel Cetina, Mario Pavelić, Sandra Kraljević Raić-Malić, Silvana Discovery of New Acid Ceramidase-Targeted Acyclic 5‑Alkynyl and 5‑Heteroaryl Uracil Nucleosides A series of novel <i>N</i>-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 <b>6</b> was shown to be more potent against MCF-7 than the reference drug 5-fluorouracil (5-FU), while C-5-alkynyl uracil derivatives <b>9c</b> and <b>9e</b> 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 <b>9c</b> and <b>9e</b> indicated that these compounds could perturb ASAH1-mediated sphingolipid signaling. The selective activity of <b>9c</b> and <b>9e</b> against breast cancer cells via the ASAH1-mediated signaling, as a molecular target, might have a great advantage for potential future therapeutic use. breast cancer cells;FU;ASAH;antibreast cancer activities;9 c;tumor cell lines;9 e;compound;uracil;MCF 2015-11-12
    https://acs.figshare.com/articles/journal_contribution/Discovery_of_New_Acid_Ceramidase_Targeted_Acyclic_5_Alkynyl_and_5_Heteroaryl_Uracil_Nucleosides/2109565
10.1021/acsmedchemlett.5b00298.s001