SYNTHESIS OF EFFECTIVE ANTICANCER THIENO [2,3-d] PYRIMIDINE-4-ONES AND THIENO [3,2-e]TRIAZOLO[4,3-c]PYRIMIDINES
نویسندگان
چکیده
In continuation to our research program concerned with structural modification of thieno[2,3-d]pyrimidines with the purpose of enhancing their anticancer activity, various series of hexahydrocycloocta[4,5]thieno[2,3-d]pyrimidin-4-ones, hexahydrocycloocta[4,5]thieno[3,2-e]-1,2,4triazolo[4,3-c]pyrimidine-3(2H)-thiones and 4-substituted hydrazinylhexahydrocycloocta[4,5]thieno[2,3-d]pyrimidines were synthesized. Most of the synthesized compounds exhibited antitumor activity against human colon carcinoma (HCT 116) cell line in vitro. Compounds 4a, 4b, 3, 12b and 5c (IC50: 11.90, 12.43, 15.91, 25.80 and 32.11 μM, respectively) exhibited 2.89 to 1.07 fold more potent antitumor activity than imatinib (IC50: 34.40 μM). Also, a docking study of the newly synthesized compounds with the active site of CDK2 was described to explore their affinity and binding mode to CDK2.
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