To explore the anticancer activity of 2, 4, 5, 6-substituted pyrimidines, several ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylate?derivatives associated with the different substituted aro...To explore the anticancer activity of 2, 4, 5, 6-substituted pyrimidines, several ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylate?derivatives associated with the different substituted aromatic/aliphatic carboxamides?and sulfonamides were synthesized. Different groups and position on phenyl ring attached to the carboxamide?and sulfonamide of the pyrimidine led to two set of compounds. Their chemical structures were confirmed by IR,1H NMR and LC/MS analysis. Cytotoxicity of all the synthesized compounds were examined on human leukemia celllines (K562 and CEM). The preliminary results showed most of the derivatives exhibited good antitumor activity. Compound?with para chloro substitution among carboxamides and compound with meta dichloro substitution among sulphonamidesexhibited significant antitumor activity with IC50 value of 14.0 μM and 15.0 μM respectively against K562cell line. For comparison among electron donating groups between carboxamides and sulfonamides, compounds with?para tert-butyl substitution were chosen for further studies. Cell cycle analysis suggests that both tert-butyl substituted?compounds are able to induce apoptosis.展开更多
文摘To explore the anticancer activity of 2, 4, 5, 6-substituted pyrimidines, several ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylate?derivatives associated with the different substituted aromatic/aliphatic carboxamides?and sulfonamides were synthesized. Different groups and position on phenyl ring attached to the carboxamide?and sulfonamide of the pyrimidine led to two set of compounds. Their chemical structures were confirmed by IR,1H NMR and LC/MS analysis. Cytotoxicity of all the synthesized compounds were examined on human leukemia celllines (K562 and CEM). The preliminary results showed most of the derivatives exhibited good antitumor activity. Compound?with para chloro substitution among carboxamides and compound with meta dichloro substitution among sulphonamidesexhibited significant antitumor activity with IC50 value of 14.0 μM and 15.0 μM respectively against K562cell line. For comparison among electron donating groups between carboxamides and sulfonamides, compounds with?para tert-butyl substitution were chosen for further studies. Cell cycle analysis suggests that both tert-butyl substituted?compounds are able to induce apoptosis.
