Utility of 6-Amino-2-thiouracil as a Precursor for the Synthesis of Pyrido[2,3-d]Pyrimidines and their in vitro and in vivo Biological Evaluation

The condensation of 6-amino-2-thiouracil 1 with aromatic aldehydes afforded azamethine derivatives 3a,b. The formed azamethines underwent [4+2] cycloaddition with enaminones 4a-c and enaminonitrile 9 to form the corresponding condensed pyrimidines 8a-f and 11a,b respectively. On the other hand the interaction of 3a,b with acetylene derivatives 12a,b, 14 afforded the corresponding pyrido[2,3-d]pyrimidine 13a-d and 16a,b respectively. The synthesized 2-azadiene 18 failed to add either electron-poor or push-pull dienophile. The in vitro antimicrobial activity of some of the newly synthesized compounds was examined. All the tested compounds proved to be active as antibacterial and antifungal agents. Also the in vivo antitumor activity of compounds 8a, 11b, 13a,d and 16b against lung (H460) and liver (HEPG2) carcinoma cells was examined. Compounds 8a, 16b showed moderate activity against lung carcinoma cell line (H460).