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

  • Bioorg Med Chem Lett. 2003 Nov 3;13(21):3841-6. doi: 10.1016/s0960-894x(03)00792-3.
Concha Sanchez-Martinez  1 ,  Chuan Shih ,  Guoxin Zhu ,  Tiechao Li ,  Harold B Brooks ,  Bharvin K R Patel ,  Richard M Schultz ,  Tammy B DeHahn ,  Charles D Spencer ,  Scott A Watkins ,  Catherine A Ogg ,  Eileen Considine ,  Jack A Dempsey ,  Faming Zhang
Affiliations
  • 1. DCR&T, Lilly Spain S.A., Avda de la Industria 30, 28108 Alcobendas, Madrid, Spain. [email protected]
PMID: 14552792 DOI: 10.1016/s0960-894x(03)00792-3
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.