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Radical-Mediated Thiol-Ene Strategy: Photoactivation of Thiol-Containing Drugs in Cancer Cells.

ABSTRACT: Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, it is shown that the activity of histone deacetylase inhibitor largazole can be switched off when stapled, but selectively switched on within cancer cells when irradiated with non-phototoxic light.

SUBMITTER: Sun S

PROVIDER: S-EPMC6391964 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Radical-Mediated Thiol-Ene Strategy: Photoactivation of Thiol-Containing Drugs in Cancer Cells.

Sun Shuang S Oliveira Bruno L BL Jiménez-Osés Gonzalo G Bernardes Gonçalo J L GJL

Angewandte Chemie (International ed. in English) 20181102 48

Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources ...[more]

PMID: 30300959

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