Click Chemistry and Multicomponent Reaction for Linker Diversification of Zinc Dipicolylamine-Based Drug Conjugates.

ABSTRACT: An efficient Ugi multicomponent reaction with strain promoted azide-alkyne cycloaddition protocol has been utilized in concert or independently to prepare a small family of bioactive zinc(II) dipicolylamine (ZnDPA)-based SN-38 conjugates. With sequential click chemistry coupling between the cytotoxic payload and phosphatidylserine-targeting ZnDPA ligand derived from structurally diverse carboxylic acids, aldehyde or ketones, and isocyanides, we demonstrated that this convergent synthetic strategy could furnish conjugates harnessing diversified linkers that exhibited different pharmacokinetic profiles in systemic circulation in vivo. Among the eight new conjugates, comparative studies on in vitro cytotoxicities, plasma stabilities, in vivo pharmacokinetic properties, an

SUBMITTER: Tsai CH 

PROVIDER: S-EPMC8886374 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature