Marine natural products as inhibitors of cystathionine beta-synthase activity. Issue 5 (1st March 2015)

• Record Type: Journal Article
• Authors: Thorson, Megan K.; Van Wagoner, Ryan M.; Harper, Mary Kay; Ireland, Chris M.; Majtan, Tomas; Kraus, Jan P.; Barrios, Amy M.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 5(2015)
• Page Start: 1070
• Page End: 1072
• Publication Date: 2015-03-01
• Subjects: CBS cystathionine beta-synthase -- CGL cystathionine gamma-lyase -- H2S hydrogen sulfide -- PLP pyridoxal-5′-phosphate -- AOAA aminooxyacetic acid -- HA hydroxylamine -- MICL Marine Invertebrate Compound Library -- AzMC 7-azido-4-methylcoumarin -- AzCC 7-azido-4-carbamoyl methyl coumarin; Hydrogen sulfide -- Sulfur metabolism -- Fluorogenic probe -- Inhibitor screen; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.01.013
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A library consisting of characterized marine natural products as well as synthetic derivatives was screened for compounds capable of inhibiting the production of hydrogen sulfide (H2 S) by cystathionine beta-synthase (CBS). Eight hits were validated and shown to inhibit CBS activity with IC50 values ranging from 83 to 187 μM. The majority of hits came from a series of synthetic polyandrocarpamine derivatives. In addition, a modified fluorogenic probe for H2 S detection with improved solubility in aqueous solutions is reported.