Synthesis of novel pyrazole-pyrimidine thioglycoside hybrids as anticancer agents

Abstract

A new series of pyrimidine thioglycosides incorporating pyrazole derivative, were synthesized via condensation of -pyrazole-4-carbaldehyde derivative 1 with substituted acetophenones 2a–d in basic medium, to afford new (E) chalcones 3a–d, the resulting compounds underwent cyclocondensation reactions with thiourea to yield sodium pyrimidine-2-thiolate derivatives 5a–d. The desired pyrimidine thioglycoside 8a–h were synthesized by the coupling of aglycone 5a-d with α-bromo per-acetylated sugars 7a,b in DMF at room temperature. On the other hand, the treatment of pyrimidine-2-thiolate salts 5a–d with HCl resulted in the formation of pyrimidine-2-thiole derivatives 6a–d. These derivatives, when stirred with α-D-gluco- and galacto-pyranosyl bromides in NaH and DMF solution produced the corresponding pyrimidine thioglycosides 8a–h. Some of the later compounds were subjected to NH₃ in methanol at 0 °C to afford the unprotected thioglycoside functionalized compounds 9a–c with good yields. Seven of newly synthesized compounds were evaluated for their anticancer activities against 2-cell lines MCF-7 (breast) and HEPG2 (liver).