Synthesis and Antitumor Evaluation of Novel Dihydropyrimidine, Thiazolo[3,2-a]pyrimidine and Pyrano[2,3-d]pyrimidine Derivatives

A simple and efficient method has been developed for the synthesis of 4,5-dihydro-2-mercapto-4-oxo-6-substituted arylpyrimidine derivatives 2a-e and their fused rings 3b, 4b, 5b, 6b and also 1,4-dihydro-2-mercaptopyrimidine derivatives 7a-e, 9a-e using triethylamine as a catalyst. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analyses. All the synthesized compounds were evaluated for their in vitro anticancer activity against six human cancer cell lines and normal fibroblasts. Nine of the tested compounds (i.e. 2a, 2c, 2d, 3b, 4b, 5b, 8, 9a and 9c) exhibited significant cytotoxicity against most cell lines. Among these derivatives compounds 2a, 3b and 9c are the most potent, they exhibited cytotoxic effect against the six cancer cell lines with IC 50 values < 330 nM compared to the standard CHS 828. Normal fibroblast cells (WI38) were affected to a much lesser extent (IC50 > 10,000 nM). Toxicity of the most potent compounds was measured against shrimp larvae; the results showed that compounds 2a and 3b are not toxic towards the tested organisms.