Baylis-Hillman Adducts as a Versatile Module for Constructing Fluorogenic Release System.

Abstract

The controlled release of a molecule of interest (MOI) is useful in probe design, prodrug construction, and drug delivery. We report herein a versatile thiol-triggered fluorogenic release system using the Baylis-Hillman (BH) adducts as a module. Common functional groups (e.g., amino, hydroxyl, carboxylic, and sulfhydryl groups) in a MOI are readily integrated into the module. The MOI release is fast (∼10 min) with a nearly quantitative yield and a >250-fold fluorescence increment. We further prepared two prodrugs to release camptothecin and nitric oxide (NO) using the two-photon excitable template, and the activation of prodrugs was visualized in live cells and mouse tissues. The therapeutic potential of the NO prodrug was also validated in a stroke model. This BH adduct-based fluorogenic release features multiple advantages, such as easy preparation, compatibility of various functional groups, fast response, high release yield, and tunable emission spectra, and is expected to have broad applications.

• Authors: Lanning Zhao, Yuan Qu, Fang Zhang, Di Ma, Hao Gao, Lu Gan, Hong Zhang, Shengxiang Zhang, Jianguo Fang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 65 Issue 8 Pg. 6056-6069 (04 28 2022) ISSN: 1520-4804 [Electronic] United States
• PMID: 35427109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prodrugs
• Sulfhydryl Compounds
• Camptothecin

Topics

• Animals
• Camptothecin
• Fluorescence
• Mice
• Prodrugs
• Sulfhydryl Compounds