Synthesis of Potent Cytotoxic Epidithiodiketopiperazines Designed for Derivatization.

ABSTRACT: We describe our design, synthesis, and chemical study of a set of functional epidithiodiketopiperazines (ETPs) and evaluation of their activity against five human cancer cell lines. Our structure-activity relationship-guided substitution of ETP alkaloids offers versatile derivatization while maintaining potent anticancer activity, offering exciting opportunity for their use as there are no examples of complex and potently anticancer (nM) ETPs being directly used as conjugatable probes or warheads. Our synthetic solutions to strategically designed ETPs with functional linkers required advances in stereoselective late-stage oxidation and thiolation chemistry in complex settings, including the application of novel reagents for dihydroxylation and cis-sulfidation of diketopiperazines. W

SUBMITTER: Olsson CR 

PROVIDER: S-EPMC7127967 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature