DFT and POM analyses of new synthesized armed pyrimidine-5-carboxylates as antitumor cytostatic agents

Abstract The research article reports on a simple synthetic strategy of ethyl 1-formyl-1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenylpyrimidine-5-carboxylates through Vilsmeier haack formylation. 1-N position is the most facile position for the formylation in these dihydro pyrimidines (DHPMs). The proposed structures of newly synthesized compounds are confirmed by spectral analysis. The compounds were screened against a broad range of human tumor cell lines; viz. Lung, Colon, Breast, Ovary, Prostate, Melanoma, CNS etc. The atomic charges, molecular geometry, as well as the drug score analyses were discussed based on POM calculations. In contrast to the introduction of –COOC 2 H 5 residue at C-5 in pyrimidine, the introduction of formyl group at N-1 position is not much beneficial for antitumor applications, while cytostatic nature of the compounds is retained. Their bioinformatic analyses indicate the coexistence of two combined pharmacophore sites. All the substituted N-formyl derivatives showed IG 50 > 100 µM which indicates that all of these compounds are cytostatic. Based on the obtained cytostatic results; by blocking antiviral pharmacophore site with metal complexes, cytotoxicity of the pyrimidine core will be targeted in the future work.