Synthesis, biological evaluation, andin silicostudies of novel chalcone- and pyrazoline-based 1,3,5-triazines as potential anticancer agents

A novel series of triazin-chalcones(7,8)a-gand triazin-N-(3,5-dichlorophenyl)pyrazolines(9,10)a-gwere synthesized and evaluated for their anticancer activity against nine different cancer strains. Triazine ketones5and6were synthesized from the cyanuric chloride1by using stepwise nucleophilic substitution of the chlorine atom. These ketones were subsequently subjected to a Claisen-Schmidt condensation reaction with aromatic aldehydes affording chalcones(7,8)a-g. Then,N-(3,5-dichlorophenyl)pyrazolines(9,10)a-gwere obtained by cyclocondensation reactions of the respective chalcones(7,8)a-gwith 3,5-dichlorophenylhydrazine. Among all the evaluated compounds, chalcones7d,gand8gexhibited more potentin vitroanticancer activity, with outstanding GI(50)values ranging from 0.422 to 14.9 mu M and LC(50)values ranging from 5.08 mu M to >100 mu M.In silicostudies, for both ligand- and structure-based, were executed to explore the inhibitory nature of chalcones and triazine derivatives. The results suggested that the evaluated compounds could act as modulators of the human thymidylate synthase enzyme.