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Vitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: synthesis, characterization and biological evaluation

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dc.contributor.authorFernández-Villa, Daniel
dc.contributor.authorAsensio, Gerardo
dc.contributor.authorSilva, Manuel
dc.contributor.authorRamírez-Jiménez, Rosa Ana
dc.contributor.authorSaldaña, Laura
dc.contributor.authorVilaboa, Nuria
dc.contributor.authorLeite-Oliveira, Ana
dc.contributor.authorRomán, Julio San
dc.contributor.authorVázquez-Lasa, Blanca
dc.contributor.authorRojo, Luis
dc.date.accessioned2021-02-02T14:19:39Z
dc.date.available2021-02-02T14:19:39Z
dc.date.issued2021
dc.description.abstractThe development of new drugs for musculoskeletal regeneration purposes has attracted much attention in the last decades. In this work, we present three novel vitamin B9 (folic acid)-derivatives bearing divalent cations (ZnFO, MgFO and MnFO), providing their synthesis mechanism and physicochemical characterization. In addition, a strong emphasis has been placed on evaluating their biological properties (along with our previously reported SrFO) using human mesenchymal stem cells (hMSC). In all the cases, pure folate derivatives (MFOs) with a bidentate coordination mode between the metal and the folate anion, and a 1:1 stoichiometry, were obtained in high yields. A non-cytotoxic dose of all the MFOs (50 μg/mL) was demonstrated to modulate by their own the mRNA profiles towards osteogenic-like or fibrocartilaginous-like phenotypes in basal conditions. Moreover, ZnFO increased the alkaline phosphatase activity in basal conditions, while both ZnFO and MnFO increased the matrix mineralization degree in osteoinductive conditions. Thus, we have demonstrated the bioactivity of these novel compounds and the suitability to further studied them in vivo for musculoskeletal regeneration applications.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFernández-Villa, D., Asensio, G., Silva, M., Ramírez-Jiménez, R. A., Saldaña, L., Vilaboa, N., ... Rojo, L. (2021). Vitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: synthesis, characterization and biological evaluation. European Journal of Medicinal Chemistry, 212, 113152pt_PT
dc.identifier.doi10.1016/j.ejmech.2021.113152pt_PT
dc.identifier.issn0223-5234
dc.identifier.urihttp://hdl.handle.net/10400.14/31864
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationMAT201573656-JINpt_PT
dc.relationRTI2018-095159-B-I00pt_PT
dc.relationPI15/00752pt_PT
dc.relationPI15/01118pt_PT
dc.relationPI18/00643pt_PT
dc.relationIND2018/BMD-9485pt_PT
dc.relationCPII16/00038pt_PT
dc.subjectMetal-folate complexespt_PT
dc.subjectStrontiumpt_PT
dc.subjectZincpt_PT
dc.subjectMagnesiumpt_PT
dc.subjectManganesept_PT
dc.subjectTissue engineeringpt_PT
dc.titleVitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: synthesis, characterization and biological evaluationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume212pt_PT
person.familyNameFernández-Villa
person.familyNameSaldaña
person.familyNameVilaboa
person.familyNameOliveira
person.familyNameRojo
person.givenNameDaniel
person.givenNameLaura
person.givenNameNuria
person.givenNameAna
person.givenNameLuis
person.identifier1415634
person.identifier.ciencia-id4713-31C8-A356
person.identifier.orcid0000-0001-7420-9104
person.identifier.orcid0000-0003-3057-4649
person.identifier.orcid0000-0003-4473-4498
person.identifier.orcid0000-0001-8012-4203
person.identifier.orcid0000-0001-6334-6736
person.identifier.ridN-2412-2014
person.identifier.ridJ-3404-2013
person.identifier.ridB-3073-2009
person.identifier.scopus-author-id57202765514
person.identifier.scopus-author-id7003366561
person.identifier.scopus-author-id6603690454
person.identifier.scopus-author-id55937245800
person.identifier.scopus-author-id15045511100
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication75c5d6b5-30b2-47a0-97f9-b2226722f02b
relation.isAuthorOfPublicationfadad898-65cd-4cb6-8a56-cadf7cbad4d0
relation.isAuthorOfPublication860a3cc1-0ff3-4186-aef2-d96de8192178
relation.isAuthorOfPublication87934068-f621-402f-b5e6-93e492526ced
relation.isAuthorOfPublication030ee915-11ea-4b87-a78c-1f4376156eae
relation.isAuthorOfPublication.latestForDiscovery87934068-f621-402f-b5e6-93e492526ced

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