Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells

In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel–thymidine and vinblastine–thymidine bi-functional conjugates are reported here. This work provides the first account of ‘kinase-mediated trapping’ of cancer therapeutics.

Graphical abstractIn the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel–thymidine and vinblastine–thymidine bi-functional conjugates are reported here. This work provides the first account of ‘kinase-mediated trapping’ of cancer therapeutics.Figure optionsDownload full-size imageDownload as PowerPoint slide