@article{fdi:010097476, title = {{L}eucettamine {B} and nacryline derivative promote the first steps of endochondral ossification in vitro}, author = {de {M}uizon, {C}. {J}. and {N}ahle, {S}. and {M}oriou, {C}. and {P}etek, {S}ylvain and {E}l {O}uazzani, {C}. and {A}l {M}ourabit, {A}. and {R}ousseau, {M}.}, editor = {}, language = {{ENG}}, abstract = {{N}owadays, there is a lack of pharmacological interventions designed to stimulate endochondral ossification ({EO}) in long bone fracture healing. {I}n the search for new active compounds, marine organisms, particularly calcarea sponges and pearl oysters were studied. {T}wo natural compounds, leucettamine {B} and nacryline, were isolated from the sponge {P}ericharax orientalis and the nacre of the pearl oyster {P}inctada margaritifera, respectively. {I}nterestingly, 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. {F}our compounds demonstrated activity on the {C}ol{X}-{M}et{L}uc-{ATCD}5 test at 0.2 m{M}. {A}mong them, pinctazole, a synthetic analog of nacryline, significantly stimulated matrix mineralization in {ATDC}5 cells. {I}n silico analysis revealed that this compound may exert multitarget and multipathway regulatory effects on {EO}. {M}olecular docking studies showed that pinctazole had the highest binding affinity to {S}rc. {A}dditionally, in silico pharmacokinetic evaluation indicated that this compound might be well absorbed. {O}verall, our results suggest that pinctazole may play a role in early events associated with {EO}, an essential process for bone repair.}, keywords = {{L}eucetammine {B} ; {S}ponges ; {N}acre ; {E}ndochondral ossification}, booktitle = {}, journal = {{S}cientific {R}eports - {N}ature}, volume = {16}, numero = {1}, pages = {18583 [14 p.]}, ISSN = {2045-2322}, year = {2026}, DOI = {10.1038/s41598-026-47546-y}, URL = {https://www.documentation.ird.fr/hor/fdi:010097476}, }