Water-soluble prodrugs of paclitaxel containing self-immolative disulfide linkers

We report here a new series of prodrugs of paclitaxel containing self-immolative disulfide linkers with improved water-solubility, in vitro anticancer activity and oral bioavailability when compared to those of paclitaxel. The disulfide bond in these prodrugs can undergo sulfhydryl-assisted cleavage to release paclitaxel in vivo by a plausible mechanism as shown in the scheme.