Synthesis and antiproliferative evaluation of novel tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrido[4,3-d]pyrimidine derivatives

Abstract

A series of tetrahydrobenzo[4′,5′]thienophene[3′,2′:5,6]pyrido[4,3-d]pyrimidine-4-(3H)-one derivatives were synthesized and evaluated for their antiproliferative activities. Biological evaluation revealed that some compounds exhibited much stronger antiproliferative activity than the positive control Fluorouracil against KB and CEN2 cell lines. Compound 7a exhibited the highest antitumor activity against KB and CNE2 cell lines with IC₅₀ values of 8.18 μM and 13.71 μM, respectively. The preliminary structure-activity relationships showed that introduction of tetrahydrobenzothieno as well as Schiff base units were favorable for the antiproliferative activity.