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Cancers
Volume 13
Issue 23
10.3390/cancers13235992
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Article

Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo

by
Aurélie Moniot
1,2,
Julien Braux
1,2,
Camille Bour
1,
Christine Guillaume
1,2,
Fabien Lamret
1,
Ingrid Allart-Simon
3,
Sandra Audonnet
4,
Sarah Renault
5,
Francoise Rédini
5,
Marie Laronze-Cochard
3,
Janos Sapi
3,6,
Sophie C. Gangloff
1,7,
Stéphane Gérard
3,6,† and
Frédéric Velard
1,2,*,†
1
EA 4691 Biomatériaux & Inflammation en Site Osseux (BIOS), SFR CAP-Santé (FED 4231), Université de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, 51096 Reims, France
2
UFR d’Odontologie, Université de Reims Champagne-Ardenne, 2 Rue du Général Koenig, 51100 Reims, France
3
UMR CNRS 7312, Institut de Chimie Moléculaire de Reims (ICMR), Université de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, 51096 Reims, France
4
Plateforme URCACyt, Université de Reims Champagne-Ardenne, 51 Rue Cognac Jay, 51096 Reims, France
5
UMR_S 1238 Sarcomes Osseux et Remodelage des Tissus Calcifiés, Phy-OS, Faculté de Médecine, Université de Nantes, 1 Rue Gaston Veil, 44035 Nantes, France
6
Campus Moulin de la Housse, UFR Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, Chemin des Rouliers, 51680 Reims, France
7
UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, 51096 Reims, France
*
Author to whom correspondence should be addressed.
†
S.G. and F.V. contributed equally to this work.
Academic Editor: Anna Maria Teti
Cancers 2021, 13(23), 5992; https://doi.org/10.3390/cancers13235992
Received: 15 October 2021 / Revised: 17 November 2021 / Accepted: 25 November 2021 / Published: 28 November 2021
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Simple Summary

There is a dire need for novel therapeutic interventions to treat osteosarcoma. Pyridazinone derivatives have proven some efficacy in several cancer models, but their effect on osteosarcoma is yet to be evaluated. Our goal was to synthesize and evaluate, both in vitro and in vivo, some pyridazinone derivatives to provide a proof of concept of their potential as anti-osteosarcoma molecules. We demonstrated that our newly synthesized pyridazinone scaffold-based molecules might be hit-candidates to develop new therapeutic avenues for multi-therapy purposes.

Abstract

Osteosarcoma is a rare primary bone cancer that mostly affects children and young adults. Current therapeutic approaches consist of combining surgery and chemotherapy but remain unfortunately insufficient to avoid relapse and metastases. Progress in terms of patient survival has remained the same for 30 years. In this study, novel pyridazinone derivatives have been evaluated as potential anti-osteosarcoma therapeutics because of their anti-type 4 phosphodiesterase activity, which modulates the survival of several other cancer cells. By using five—four human and one murine osteosarcoma—cell lines, we demonstrated differential cytotoxic effects of four pyridazinone scaffold-based compounds (mitochondrial activity and DNA quantification). Proapoptotic (annexin V positive cells and caspase-3 activity), anti-proliferative (EdU integration) and anti-migratory effects (scratch test assay) were also observed. Owing to their cytotoxic activity in in vitro conditions and their ability to limit tumor growth in a murine orthotopic osteosarcoma model, our data suggest that these pyridazinone derivatives might be hit-candidates to develop new therapeutic strategies against osteosarcoma. View Full-Text
Keywords: osteosarcoma; pyridazinone; cytotoxicity; migration; tumor growth osteosarcoma; pyridazinone; cytotoxicity; migration; tumor growth
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MDPI and ACS Style

Moniot, A.; Braux, J.; Bour, C.; Guillaume, C.; Lamret, F.; Allart-Simon, I.; Audonnet, S.; Renault, S.; Rédini, F.; Laronze-Cochard, M.; Sapi, J.; Gangloff, S.C.; Gérard, S.; Velard, F. Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo. Cancers 2021, 13, 5992. https://doi.org/10.3390/cancers13235992

AMA Style

Moniot A, Braux J, Bour C, Guillaume C, Lamret F, Allart-Simon I, Audonnet S, Renault S, Rédini F, Laronze-Cochard M, Sapi J, Gangloff SC, Gérard S, Velard F. Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo. Cancers. 2021; 13(23):5992. https://doi.org/10.3390/cancers13235992

Chicago/Turabian Style

Moniot, Aurélie, Julien Braux, Camille Bour, Christine Guillaume, Fabien Lamret, Ingrid Allart-Simon, Sandra Audonnet, Sarah Renault, Francoise Rédini, Marie Laronze-Cochard, Janos Sapi, Sophie C. Gangloff, Stéphane Gérard, and Frédéric Velard. 2021. "Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo" Cancers 13, no. 23: 5992. https://doi.org/10.3390/cancers13235992

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