Aim: Due to emergence of resistance to available anticancer agents, there is a need to search for new cytotoxic agents. Methods: Pyrido[2,3- d]pyrimidines (4–6) and their tricyclic derivatives (7–13) were prepared and screened for their cytotoxicity against breast MCF-7, prostate PC-3 and lung A-549 cancer cell lines as well as normal fibroblasts WI-38. Results: The most active compounds were 6b, 6e and 8d compared with doxorubicin. Moreover, compounds 6b and 8d induced apoptosis in PC-3 and MCF-7, respectively via activation of CASP3 (in PC-3 only), Bax, p53 and down regulation of Bcl2 in addition to CDK4/6 inhibition. Conclusion: Pyrido[2,3- d]pyrimidine represents an important core for discovery of new potent cytotoxic agents acting on the cell cycle via apoptosis induction through either intrinsic or extrinsic pathways.
ABSTRACT. The reaction of 2-amino-3-cyano-tetrahydrobenzothiophene 3 with ethyl acetoacetate gave the amide derivatives 5. The reactivity of 5 toward a variety of chemical reagents was studied to give pyrans, pyridines, thiophenes and the thiazoles and their fused derivatives. The structures of the newly synthesized products were confirmed on the basis of their respective analytical and spectral data. The antitumor evaluations of the synthesized compounds against the three cancer cell lines MCF-7, NCI-H460 and SF-268 showed that compounds 9a, 9c, 12a and 14 were of the highest potencies against the three cancer cell lines among the tested compounds.
The hydrazide-hydrazone 3 reacted with benzenediazonium chloride to give the phenylhydrazone derivative 5. The latter underwent a series of heterocyclization reactions to give pyridazine, 1,2,3-triazole and pyrazole derivatives. The antitumor evaluation of the newly synthesized products against the three cancer cells lines namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer showed that some of them have higher inhibitory effects towards the three cell lines compared to the standard.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.