Azobenzene-containing photoswitchable proteasome inhibitors with selective activity and cellular toxicity. Issue 19 (1st October 2017)

• Record Type: Journal Article
• Authors: Blanco, Beatriz; Palasis, Kathryn A.; Adwal, Alaknanda; Callen, David F.; Abell, Andrew D.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 19(2017)
• Page Start: 5050
• Page End: 5054
• Publication Date: 2017-10-01
• Subjects: Proteasome inhibitors -- Azobenzenes -- Photopharmacology; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.06.011
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of azobenzene-containing peptidic boronate esters was prepared and the activity of the thermally adapted states (TAS), enriched in trans isomer, and the photostationary states (PSS), enriched in cis isomer, for each compound were evaluated against β5 and β1 proteasome subunits. Compounds with a sterically demanding phenyl-substituted azobenzene at P2 (4c ), and a less sterically demanding unsubstituted azobenzene at the N -terminus (5a ), showed the greatest difference in activity between the two states. In both cases, the more active trans -enriched TAS had activity comparable to bortezomib and delanzomib. Furthermore, cis -enriched 4c inhibited tumor growth in both breast and colorectal carcinoma cell lines. Significantly, the initial trans -enriched TAS of 4c was not cytotoxic against the non-malignant MCF-10A cells.