ANTIPROLIFERATIVE ACTION OF PYRROLOBENZOXAZEPINE DERIVATIVES IN CULTURED-CELLS - ABSENCE OF CORRELATION WITH BINDING TO THE PERIPHERAL-TYPEBENZODIAZEPINE BINDING-SITE

Three novel peripheral-type benzodiazepine binding site (PBBS) ligands , NF 182, 213 and 262, along with the classically used PBBS ligands, P K 11195 and Ro5-4864, were found to inhibit, at micromolar concentrati ons and in dose dependent manner, the proliferation of rat C6 glioma a nd human 1321N1 astrocytoma, without being cytotoxic. This antiprolife rative effect is mediated by arrest in the G1 phase of the cell cycle and does not appear to be mediated by a specific interaction of these ligands with the peripheral-type benzodiazepine binding site. (C) 1998 Elsevier Science Inc.