STUDY OF THE ANTI-TUMOR ACTIVITY OF SYNTHETIC PYRIDO [2,3-d]PYRIMIDINES, PYRIMIDINES AND CORRESPONDING CHALCONE DERIVATIVES

Chalcones (3a-m) was prepared by condensing 4-aminoacetophenone (1) with various aromatic aldehydes (2a-m) according to Claisen-Schmidt condensation. These 4-aminochalcones on cyclization with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines 4a-m with quantitative yields. Novel 4-amino-5,7-disubstituted pyrido[2,3-d]pyrimidines 6a-g were synthesized via a facile regioselective cyclization followed by aromatization of 2-amino-3-cyano-4,6-disubstitutedpyridines 5a-k which were in turn prepared from 4-aminochalcones 3a-m. All the synthesized compounds were characterized by spectroscopic means (FT-IR, ¹H and ¹³C NMR, LC-MS) and elemental analysis and screened for anticancer activity by in-vitro MTT assay against Hos, HT 29, G 361, A 549 and DU 145 cell lines. Pyridopyrimidine nucleus was found to be the best pharmacophore than chalcone and pyrimidine nucleus in cancer therapy. And also it was found that compounds which possess  2,4-dichlorophenyl (3b,4b and 6b), 4-fluorophenyl (4c and 6c) and 4-dimethylamino (3i,4i and 6g) moieties as substituent at respective position in chalcones, pyrimidines and pyrido[2,3-d]pyrimidines identified as lead molecules. All the molecules were found to possess better activity against Hos (bone cancer) and G 361 (human skin cancer) cell lines.