Multicomponent Synthesis, Characterization of Novel Pyrimidine Derivatives with Anti-cancer Potential

Abstract:

Background: Search for the better anti-cancer agents become central part for many research teams as the current drugs in use suffer lack of specificity to the cancer targets. Design and development of target specific anti-cancer agents increase the potency and safety of the drugs. Materials and Methods: Current research intends to develop a novel series of the pyrimidine derivatives owing to the anti-cancer potential of the pyrimidine scaffold. In a multicomponent reaction approach, 4,5-disubstituted pyrimidines (4) were synthesized from three component coupling reaction of substituted enamine (1), an orthoester (triethoxy methane) (2) and ammonium acetate (3). 4,5-disubstituted pyrimidines (4) were oxidized to corresponding aldehyde derivative (5) via Stephen aldehyde synthetic process. Then the pyrimidine aldehyde coupled with various aromatic amines to produce final pyrimidine imine derivatives (6a-6j). By using IR, 1H-NMR, and mass spectral studies, all the prepared derivatives were characterized and subjected to anti-cancer activity evaluation by MTT Assay. Four cancer cells (A 549 (lung), B16F10 (mouse skin melanoma), SiHA (cervical), MCF-7 (breast), and one normal fibroblast (L929)] were employed to study the anti-cancer potential of the synthesized pyrimidine derivatives. Results: The synthesized compounds produced in moderate to good yields with proposed scheme of synthesis. All the synthesized derivatives displayed noticeable cytotoxicity against the tested cancer cell lines. Conclusion: All of the evaluated cell lines were susceptible to the potential cytotoxicity of the newly synthesized novel pyrimidine derivative. These brand-new pyrimidine compounds may be transformed into potent anti-cancer lead molecules.

Keywords: Multicomponent synthesis, Pyrimidines, Anti-cancer, MTT Assay.