Synthesis of new pyrimidine derivatives and their antiproliferative activity against selected human cancer cell lines

Abstract

6-Amino-2-thiouracil (1) was condensed with benzenesulfonyl chloride and p-toluenesulfonyl chloride in presence of pyridine as an acid binder to give sulfonamides 2a, b, which could be methylated in basic medium to give methylmercapto derivatives 3a, b, which in turn reacted with bromine in glacial acetic acid to yield 5-bromo derivatives 4a, b. On the other hand, compounds 2a, b were cyclocondensed with monochloroacetyl chloride, p-tolualdehyde in glacial acetic acid/ pyridine, and ethyl bromoacetate to give the corresponding thiazolopyrimidines 5a, b, 6a, b, and 7a, b, respectively; also compounds 2a, b were hydrazinolyzed to compounds 8a, b, which could be cyclized to triazolopyrimidines 9a, b in presence of formic acid. They could also be condensed with p-anisaldehyde to give hydrazones 10a, b. In another pathway, compounds 2a, b were reacted with monochloroacetic acid in basic medium to give acetic acid derivatives 11a, b. It can be deduced from the preliminary screening results that the cell lines most sensitive to the antiproliferative activity of tested compounds are human liver HEPG2 and colon cancer HT-29. All selected compounds exhibited moderate to strong growth inhibition activity against the HEPG2 cell line with 50 % inhibitory concentration (IC 50 ) ranging between 1 and 10 lg/ml. The most active compounds, which revealed antiproliferative activity also against human colon HT-29 and breast MCF-7 cell lines, were 3a, 3b, 4a, and 10a.

Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone‐Thienopyrimidine Derivatives in HepG2 and MCF‐7 Cell Lines

“…Bagul et al [ 54 ] found that chalcone-linked pyrazoloij1,5-a] pyrimidine hybrids induced antiproliferative actions when incubated in vitro with MDA-MB-231 (breast cancer), -549 (lung cancer), and DU-145 (prostate cancer) cells and that the results were comparable with the used reference treatment (erlotinib). Moreover, thiopyrimidines were studied against leukemia and colon and breast cell lines, and the results indicated promising antitumor activities [ 55 ]. In addition, some novel morpholinylchalcone (the building blocks for the formation of a series of pyridopyrimidinethiones and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones) synthesized compounds were observed to induce significant anticancer actions equivalent to the standard treatment cisplatin when applied in vitro against A-549 and HepG-2 cells [ 56 ].…”

Cytotoxic Effects of Thiazolo[3,2-C]Pyrimidines Against Mcf-7 And Hepg2/C3a Carcinoma Cell Lines

“…Similarly, p-MeO, p-Cl-phenyl substituted arylthiazolopyrimidines displayed very strong cytotoxic effects against MCF-7 cell lines [16]. In addition, phenylsulfonamidosubstituted thiazolo [3,2-a]pyrimidines demonstrated very significant antitumor activities against colon cancer-HT-29, human liver-HEPG2 and MCF-7 cell lines at very low concentrations [34]. Also, some aryl and benzyl substituted 2-thioxothiazolo [4,5-d]pyrimidinones were found to be significantly active against lung-NCI-H-460, breast-MCF-7 and CNS-SF-268 cancer cell lines [35].…”

Thiopyrimidine‐5‐carbonitrile Derivatives as VEGFR‐2 Inhibitors: Synthesis, Anticancer Evaluation, Molecular Docking, ADME Predictions and QSAR Studies

“…[27][28][29][30][31] Reports demonstrated that 5cyano-2-thiouracils and thiouracils, result in an anticancer activity against many human cancer cells, for instance; liver (HEPG-2), breast (MCF-7), colon (HCT-116, HT-29, and CaCo-2), renal cancer (HELa), leukemia (MOLT-4), and cervical cancer. [32][33][34][35] Moreover, literature survey revealed that thiouracil carbonitrile ring occupied a prominent position in the design and synthesis of new chemotherapeutic agents that have a remarkable antitumor activity ( Figure 1). For example, thiouracil quinoxaline hybrids I showed a strong inhibitory effect, against carcinogenesis on Raji cells.…”

“…One of these compounds, 2‐thioxopyrimidine derivatives which were brought into research scope by many synthetic‐biochemists [27–31] . Reports demonstrated that 5‐cyano‐2‐thiouracils and thiouracils, result in an anticancer activity against many human cancer cells, for instance; liver (HEPG‐2), breast (MCF‐7), colon (HCT‐116, HT‐29, and CaCo‐2), renal cancer (HELa), leukemia (MOLT‐4), and cervical cancer [32–35] . Moreover, literature survey revealed that thiouracil carbonitrile ring occupied a prominent position in the design and synthesis of new chemotherapeutic agents that have a remarkable antitumor activity (Figure 1).…”