SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF NEW FUSED TRIAZINE DERIVATIVES BASED ON 6-METHYL-3-THIOXO-1,2,4-TRIAZIN-5-ONE

A one-pot reaction of 6-methyl-3-thioxo-3,4-dihydro-[1,2,4]triazin-5-one 1 with selected aldehydes 2a-d and chloroacetic acid afforded the respective 2-arylidene-6-methyl-thiazolo[3,2-b][1,2,4]triazine-3,7-diones 4a-d. Compunds 4a-d could be also obtained via the reaction of 1 with chloroacetic acid in refluxing acetic acid to give 6-methyl-thiazolo[3,2-b][1,2,4]triazine-3,7-dione 3 then, Knoevenagel condensation of 3 with aldehydes 2a-d gave compounds 4a-d. Heterocyclization of 4a-c with hydrazine hydrate and phenylhy- drazine gave the corresponding pyrazolines 5a-c and 6a-c, respectively. Moreover, 7-amino-9-(aryl)-3-methyl-2-oxo-2H-pyrido[2',3':4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-8-carbonitrles 7a-c were synthesized by the reaction of 4a-c with malononitrile in the presence of ammonium acetate. The structures of newly synthesized compounds were confirmed by analytical and spectroscopic measurements. Some selected new compounds were screened for their cytotoxic activities against three human cancer cell lines (HepG2, MCF-7 and A549) using SRB assay and the structure-activity relationship (SAR) was discussed. The biochemical assays including antioxidant enzyme, oxidative stress and estimation of nucleic acids and proteins have been discussed for some selected compounds. The molecular docking of 4c and 7b has been also studied.