Chemical Investigation of the Calcareous Marine Sponge Pericharax heteroraphis , Clathridine-A Related Derivatives Isolation, Synthesis and Osteogenic Activity.

Autor: Jourdain de Muizon C; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Moriou C; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Levasseur M; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Touboul D; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.; Laboratoire de Chimie Moléculaire (LCM), CNRS, École Polytechnique, Institut Polytechnique de Paris, 91120 Palaiseau, France., Iorga BI; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Nedev H; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Van Elslande E; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Retailleau P; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France., Petek S; IRD, CNRS, Ifremer, Univ Brest, LEMAR, IUEM, 29280 Plouzane, France., Folcher E; IRD, SEOH, BPA5, Nouméa 98848, New Caledonia., Bianchi A; Université de Lorraine, 54000 Nancy, France., Thomas M; SAINBIOSE U1059, INSERM, Mines Saint Etienne, Université Jean Monnet Saint-Etienne, 42023 Saint-Etienne, France., Viallon S; SAINBIOSE U1059, INSERM, Mines Saint Etienne, Université Jean Monnet Saint-Etienne, 42023 Saint-Etienne, France., Peyroche S; SAINBIOSE U1059, INSERM, Mines Saint Etienne, Université Jean Monnet Saint-Etienne, 42023 Saint-Etienne, France., Nahle S; SAINBIOSE U1059, INSERM, Mines Saint Etienne, Université Jean Monnet Saint-Etienne, 42023 Saint-Etienne, France., Rousseau M; SAINBIOSE U1059, INSERM, Mines Saint Etienne, Université Jean Monnet Saint-Etienne, 42023 Saint-Etienne, France.; UMR5510 MATEIS, CNRS, INSA-Lyon, University of Lyon, 69621 Lyon, France., Al-Mourabit A; CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
Jazyk: angličtina
Zdroj: Marine drugs [Mar Drugs] 2024 Apr 25; Vol. 22 (5). Date of Electronic Publication: 2024 Apr 25.
DOI: 10.3390/md22050196
Abstrakt: As a result of screening a panel of marine organisms to identify lead molecules for the stimulation of endochondral bone formation, the calcareous sponge Pericharax heteroraphis was identified to exhibit significant activity during endochondral differentiation. On further molecular networking analysis, dereplication and chemical fractionation yielded the known clathridine A-related metabolites 3-6 and the homodimeric complex (clathridine A) 2 Zn 2+ ( 9 ), together with the new unstable heterodimeric complex (clathridine A-clathridimine)Zn 2+ ( 10 ). With the presence of the zinc complexes annotated through the LC-MS analysis of the crude extract changing due to the instability of some metabolites and complexes constituting the mixture, we combined the isolation of the predicted molecules with their synthesis in order to confirm their structure and to understand their reactivity. Interestingly, we also found a large quantity of the contaminant benzotriazoles BTZ ( 7 ) and its semi-dimer (BTZ) 2 CH 2 ( 8 ), which are known to form complexes with transition metals and are used for preventing corrosion in water. All isolated 2-aminoimidazole derivatives and complexes were synthesized not only for structural confirmation and chemical understanding but to further study their bioactivity during endochondral differentiation, particularly the positively screened imidazolone derivatives. Compounds leucettamine B, clathridine A and clathridimine were found to increase type X collagen transcription and stimulate endochondral ossification in the ATDC5 micromass model.
Databáze: MEDLINE
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