title: Marine natural products as inhibitors of cystathionine beta-synthase activity.
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 (H2S) by cystathionine beta-synthase (CBS). Eight hits were validated and shown to inhibit CBS activity with IC50 values ranging from 83 to 187μM. The majority of hits came from a series of synthetic polyandrocarpamine derivatives. In addition, a modified fluorogenic probe for H2S detection with improved solubility in aqueous solutions is reported.
authors: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
authors: Megan K
authors: MK
authors: Thorson
authors: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
authors: Ryan M
authors: RM
authors: Van Wagoner
authors: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
authors: Mary Kay
authors: MK
authors: Harper
authors: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
authors: Chris M
authors: CM
authors: Ireland
authors: Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA.
authors: Tomas
authors: T
authors: Majtan
authors: Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA.
authors: Jan P
authors: JP
authors: Kraus
authors: Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA. Electronic address: amy.barrios@utah.edu.
authors: Amy M
authors: AM
authors: Barrios
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000032:analysis / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D014561:Urochordata / Q000737:chemistry*
chemical_list: D000588:Amines; D001688:Biological Products; D004791:Enzyme Inhibitors; D007093:Imidazoles; C588236:polyandrocarpamine A; C588235:polyandrocarpamine B; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Fluorogenic probe; Hydrogen sulfide; Inhibitor screen; Sulfur metabolism