title: Cyclotheonellazoles A-C, Potent Protease Inhibitors from the Marine Sponge Theonella aff. swinhoei.
abstract: The extract of a sample of the sponge Theonella aff. swinhoei collected in Madagascar exhibited promising in vitro antiplasmodial activity. The antiplasmodial activity was ascribed in part to the known metabolite swinholide A. Further investigation of the extract afforded three unusual cyclic peptides, cyclotheonellazoles A-C (1-3), which contain six nonproteinogenic amino acids out of the eight acid units that compose these natural products. Among these acids the most novel were 4-propenoyl-2-tyrosylthiazole and 3-amino-4-methyl-2-oxohexanoic acid. The structure of the compounds was elucidated by interpretation of the 1D and 2D NMR data, HRESIMS, and advanced Merfay's techniques. The new compounds were found to be nanomolar inhibitors of chymotrypsin and sub-nanomolar inhibitors of elastase, but did not present antiplasmodial activity.
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Ramat Aviv, Tel-Aviv 69978, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Issac
authors.affiliation: Laboratoire de Chimie des Substances Naturelles et des Aliments, Faculté des Sciences et Technologies, Université de La Réunion , 15 Avenue René Cassin, CS 92 003, 97 744, Saint-Denis, Cedex 9, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Aknin
authors.affiliation: Laboratoire de Chimie des Substances Naturelles et des Aliments, Faculté des Sciences et Technologies, Université de La Réunion , 15 Avenue René Cassin, CS 92 003, 97 744, Saint-Denis, Cedex 9, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gauvin-Bialecki
authors.affiliation: Naturalis Biodiversity Center , P.O. Box 9517, 2300 RA, Leiden, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: De Voogd
authors.affiliation: Laboratory of Pharmacognosy, Department of Pharmacy, CIRM, University of Liège , B36, 4000 Liège, Belgium.
authors.forename: Alisson
authors.identifier: 0000-0002-4052-6336
authors.initials: A
authors.lastname: Ledoux
authors.affiliation: Laboratory of Pharmacognosy, Department of Pharmacy, CIRM, University of Liège , B36, 4000 Liège, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Frederich
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Ramat Aviv, Tel-Aviv 69978, Israel.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kashman
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University , Ramat Aviv, Tel-Aviv 69978, Israel.
authors.forename: Shmuel
authors.identifier: 0000-0002-9641-9943
authors.initials: S
authors.lastname: Carmeli
mesh_terms: D000818:Animals; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D008270:Madagascar; D008386:Marine Biology; D008387:Marine Toxins / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047232:Theonella / Q000737:chemistry*
chemical_list: D008387:Marine Toxins; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C000621400:cyclotheonellazole A; C000621401:cyclotheonellazole B; C000621402:cyclotheonellazole C; C086235:swinholide A; D002918:Chymotrypsin; D010196:Pancreatic Elastase