Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines

A library of 42 diastereoisomeric mixtures of fumitremorgin-type indolyl diketopiperazines, prepared by parallel solid-phase synthesis, was screened for Breast Cancer Resistance Protein inhibitory activity and compared with GF120918. Demethoxy-fumitremorgin C was synthesized by solid-phase techniques and tested as well. Structure–activity relationship studies have identified several potent analogues, both in assays using the T6400 mouse and the T8 human cell line, whereas low cytotoxicity was seen at effective concentrations