Title of article :
Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides
Author/Authors :
Concha Sanchez-Martinez، نويسنده , , Chuan Shih، نويسنده , , Guoxin Zhu، نويسنده , , Tiechao Li، نويسنده , , Harold B. Brooks، نويسنده , , Bharvin K.R. Patel، نويسنده , , Richard M. Schultz، نويسنده , , Tammy B. DeHahn، نويسنده , , Charles D. Spencer، نويسنده , , Scott A. Watkins، نويسنده , , Catherine A. Ogg، نويسنده , , Eileen Considine، نويسنده , , Jack A. Dempsey، نويسنده , , Faming Zhang، نويسنده ,
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.
