Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides

Abstract A series of indolo[2,3- a ]pyrrolo[3,4- c ]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1–CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3- a ]pyrrolo[3,4- c ]carbazoles are consistently more active (8–42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.