New thiophene analogues of kenpaullone: synthesis and biological evaluation in breast cancer cells.

Thieno analogues of kenpaullone have been synthesized using an established method. We investigated the effect of five structural analogues of kenpaullone on vincristine sensitive and resistant MCF7 (human mammary adenocarcinoma) cells. One analogue, 8-Bromo-6,11-dihydro-thieno-[3',2':2,3]azepino[4,5-b]indol-5(4H)-one (3a), showed an antiproliferative activity in the drug sensitive cell line that led to cell accumulation in G2/M phase. In addition, repression of cdk1, a G2/M transition key regulator, as well as induction of p21 were observed at the mRNA level. Programmed cell death (apoptosis) was induced in early time treatments and was accompanied by p53 mRNA induction. The antiproliferative and proapoptotic properties of 3a make this CDK inhibitor an interesting candidate for further investigations.