Synthesis and anticancer activity of novel 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine derivatives

A series of new 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines with different substituents as C-4 position was synthesized. The anticancer activity of the newly synthesized compounds was tested in vitro using a two-stage process utilizing 60 different human tumor cell lines representing leukemia, melanoma and cancers of lung, colon, central nervous system, ovary, kidney, prostate as well as breast. Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity at low concentrations against most of the used human tumor cell lines comparable with doxorubicin as standard potent anticancer drug (average log10 GI50 over all cell lines = −6.85). Also, compound 4b was selective against SNB-75 (CNS cancer) log10 GI50 = −5.57. Interestingly, compound 7e exhibited promising selectivity against 13 tumor cell lines showing growth inhibition percentages between 54.05 and 89.23.

Graphical abstractSynthesis and anticancer activity of a series of new 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines with different substituents as C-4 position are presented.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of new thieno[2,3-d]pyrimidines was synthesized. ► The anticancer activity of the new compounds was tested in vitro. ► Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity. ► Compounds 4b, 5a and 7e exhibited promising anticancer activity. ► Substitutions at positions 2 and 4 showed an effect on the anticancer activity.