Thiol-Michael addition based conjugate for glutathione activation and release

A thiol-Michael addition based conjugate TC6 for glutathione activation and release was reported. TC6 was easily synthesized and showed high selectivity to glutathione with relative stability. [Display omitted] •A thiol-Michael addition based GSH response conjugate TC6 was reported.•TC6 is easily synthesized and showed good selectivity to glutathione with certain stability.•The camptothecin release experiment of TC6 showed improved anti-tumor ability in vitro and in vivo. Glutathione (GSH) level has long been recognized as a valuable tumor biomarker. GSH-mediated activation and release systems have been extensively developed for cancer diagnosis and treatment, but mainly focused on disulfide-based conjugate. We reported here a new thiol-Michael addition based GSH response conjugate TC6, which consists of a unique tricyclic structure containing α, β-unsaturated ketone responsive groups. The conjugate was easily synthesized and showed good selectivity to glutathione with certain stability. The camptothecin delivery experiment of TC6 showed improved anti-tumor ability in cells and tumor-bearing mice. TC6 could be used for the development of antibody or small molecule conjugated drugs.