61736-36-5Relevant academic research and scientific papers
Pyrimidine-2,4-dione targets STAT3 signaling pathway to induce cytotoxicity in hepatocellular carcinoma cells
Sajith, Ayyiliath M,Narasimhamurthy, Kereyagalahally H.,Shanmugam, Muthu K.,Rangappa, Shobith,Chandra Nayak,Chinnathambi, Arunachalam,Awad Alahmadi, Tahani,Ali Alharbi, Sulaiman,Haridas,Reddy,Savitha,Mohan, Chakrabhavi Dhananjaya,Rangappa, Kanchugarakoppal S.
, (2021)
Signal transducer and activator of transcription 3 (STAT3) is a tumorigenic transcription factor that is persistently activated in various human cancers including hepatocellular carcinoma (HCC). Therefore, STAT3 is considered as a prominent target to counteract the uncontrolled proliferation of cancer cells. In the present report, pyrimidine-2,4-diones (N-methyluracil derivatives) (MNK1-MNK14) were synthesized in an ionic liquid (BMIm PF6) medium employing a ligand-free Suzuki-Miyaura cross-coupling process. Among the 14 derivatives, compound MNK8 showed good cytotoxicity towards both the tested cell lines and did not display a toxic effect against normal hepatocytes (LO2). MNK8 significantly increased the Sub-G1 cell count in both cell lines and the cytotoxic effect of MNK8 was found to be mediated through the suppression of constitutive phosphorylation of STAT3Y705. It also decreased the DNA interaction ability of nuclear STAT3 in HCC cells. MNK8 downregulated the levels of apoptosis-related proteins (such as Bcl-2, cyclin D1, survivin) and increased cleaved caspase-3 inferring the apoptogenic effect of MNK8. It also reduced the CXCL12-triggered cell migration and invasion in in vitro assay systems. Overall, MNK8 has been demonstrated as a new inhibitor of STAT3 signaling cascade in HCC cells.
Direct Chemoselective Synthesis of N-3-Substituted Pyrimidinones in a Microwave-Assisted Method
Laxminarayana, Burgula,Kundu, Lal Mohan
supporting information, p. 1342 - 1353 (2015/05/26)
Synthesis of selectively N-3-substituted pyrimidine nucleobases or pyrimidinones has always been a challenge because of poor regioselectivity and chemoselectivity. In this article we demonstrate a single-step, de novo synthesis of selectively N-3-substitu
Synthesis of uracil derivatives by oxidation of Fischer tungsten-carbene uracil complexes
Sala, Giorgio Della,Artillo, Antonietta,Ricart, Susagna,Spinella, Aldo
, p. 1623 - 1627 (2007/10/03)
A study on the oxidation of Fischer tungsten-carbene uracil complexes has been carried out. Several commonly used oxidants gave results strongly influenced by the presence of substituent on nitrogen atoms. In particular, usual oxidants failed in the oxidation of 3-alkyl uracil carbene complexes. Finally, we showed that t-butyl hydroperoxide is able to oxidize successfully also 3-alkyl uracil carbene complexes and can be used as a good alternative to the other methods.
