Work

Photoswitchable anticancer activity via trans–cis isomerization of a combretastatin A-4 analog

Year: 2015

Type: article

Abstract: Combretastatin A-4 (CA4) is highly potent anticancer drug that acts as an inhibitor of tubulin polymerization. The core of the CA4 structure contains a cis-stilbene, and it is known that the trans isomer is significantly less potent. We prepared an azobenzene analog of CA4 (Azo-CA4) that shows 13-35 fold enhancement in potency upon illumination. EC50 values in the light were in the mid nM range. Due to its ability to thermally revert to less toxic trans form, Azo-CA4 also has the ability to automatically turn its activity off with time. Azo-CA4 is less potent than CA-4 because it degrades in the presence of glutathione as evidenced by UV-Vis spectroscopy and ESI-MS. Nevertheless, Azo-CA4 represents a promising strategy for switchable potency for treatment of cancer.

Source: Organic & Biomolecular Chemistry

DOI: 10.1039/c5ob02005k

Authors: Jonathon E. Sheldon, M. Michael Dcona, Charles E. Lyons, John C. Hackett, Matthew C. T. Hartman

Institutions: Virginia Commonwealth University, VCU Massey Comprehensive Cancer Center

Language: English

Topic: Photochromic and Fluorescence Chemistry

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Cancer Institute, National Institute of General Medical Sciences