Regioselective synthesis and initial evaluation of a folate receptor targeted rhaponticin prodrug

To improve the therapeutic effect of rhaponticin (RHA), a folate receptor (FR) targeted RHA prodrug was designed and regioselectively synthesized by utilizing a hydrophilic peptide spacer linked to folic acid (FA) via a releasable disulfide linker. A series of biological evaluation was investigated in vitro and in vivo. The positive results of biological investigations warrant further preclinical study before this novel targeted chemotherapeutic is considered for clinical investigation.