Background: Pyrimidinones and its derivatives are present in many anti-cancer agents. It has
been reported that these substances were proven to have significant activities against different types of
human cancers. The incorporation of [1,2,3]-triazole, a nitrogen-rich unit not only increases the efficacy
but also increases the lipophilicity of the drug molecule. As our research was to synthesize newer molecules
of effective cytotoxicity, we focused on pyrimidinone and [1,2,3]-triazoles systems, as important
scaffolds with the expectation of potential cytotoxic properties.
Methods: Novel series of [1,2,3]-triazole carboxamides (5a-j) were synthesized, starting from 3-(2-
chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. The structure of all the synthesized
compounds was elucidated based on IR, 1H-NMR, 13C-NMR and LC-MS data. Compounds were
focused for their in vitro cytotoxicity against A375 melanoma cancer cell lines, MDA-MB-231 breast
cancer cell lines and HEK 293-Human embryonic kidney cell lines using colorimetric MTT assay. The
potent compound was evaluated for the DNA binding studies.
Results: Most of the Pyrimidinone conjugated [1,2,3]-triazole carboxamides found to be selective towards
melanoma cancer cell lines than breast cancer cell lines. Compounds 5d, 5i and 5b were effective
against A375 cancer cell lines and are found to be non-toxic against HEK 293-Human embryonic kidney
cell lines. The potent compound 5d showed good intrinsic binding constant (Kb) value 3.12 x 103
M-1 in UV based DNA titration.
Conclusion: Newly synthesized Pyrimidinone conjugated [1,2,3]-triazole carboxamide derivatives
showed the significant cytotoxicity and the potent compound showed good intrinsic binding constant in
UV based DNA titration.