Synthesis and evaluation of a fluorescent ritterazine-cephalostatin hybrid

The cephalostatin and ritterazine natural products comprise a potent family of bis-steroidal pyrazines that display potent single-digit nanomolar inhibition of tumor cell growth. An active fluorescent ritterazine-cephalostatin hybrid probe was developed using detailed SAR data derived through total synthetic efforts. A combination of time course and confocal imaging studies indicate that this natural product family is rapidly taken up in tumor cells and localizes subcellularly within ER and surrounding the nuclear-ER interface.