de Muizon C. J. auteur aut IRD Nahle S. auteur aut IRD Moriou C. auteur aut IRD Petek Sylvain auteur aut IRD El Ouazzani C. auteur aut IRD Al Mourabit A. auteur aut IRD Rousseau M. auteur aut IRD text journalArticle eng text/pdf reformatted digital access Nowadays, there is a lack of pharmacological interventions designed to stimulate endochondral ossification (EO) in long bone fracture healing. In the search for new active compounds, marine organisms, particularly calcarea sponges and pearl oysters were studied. Two natural compounds, leucettamine B and nacryline, were isolated from the sponge Pericharax orientalis and the nacre of the pearl oyster Pinctada margaritifera, respectively. Interestingly, leucettamine B and nacryline exhibit significant structural similarities. A library of derivatives of both molecules was synthesized. A new synthetic pathway was developed to access leucettamine B and its derivatives via late-functionalization. Four compounds demonstrated activity on the ColX-MetLuc-ATCD5 test at 0.2 mM. Among them, pinctazole, a synthetic analog of nacryline, significantly stimulated matrix mineralization in ATDC5 cells. In silico analysis revealed that this compound may exert multitarget and multipathway regulatory effects on EO. Molecular docking studies showed that pinctazole had the highest binding affinity to Src. Additionally, in silico pharmacokinetic evaluation indicated that this compound might be well absorbed. Overall, our results suggest that pinctazole may play a role in early events associated with EO, an essential process for bone repair. specialized Leucetammine B Sponges Nacre Endochondral ossification 035 034 020 16 1 18583 [14 p.] 2026 2045-2322 https://www.documentation.ird.fr/hor/fdi:010097476 10.1038/s41598-026-47546-y 2045-2322 [F B010097476] https://www.documentation.ird.fr/hor/fdi:010097476 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2026-07/010097476.pdf IRD - Base Horizon / Pleins textes 2026-07-09 2026-07-09 fdi:010097476 fre