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

Autor: Fernández-Villa D; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain., Asensio G; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain., Silva M; Universidade Católica Portuguesa - Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, 4169-005, Porto, Portugal., Ramírez-Jiménez RA; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain., Saldaña L; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, 28029, Madrid, Spain., Vilaboa N; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, 28029, Madrid, Spain., Leite-Oliveira A; Universidade Católica Portuguesa - Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, 4169-005, Porto, Portugal., San Román J; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain., Vázquez-Lasa B; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain., Rojo L; Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas (ICTP-CSIC), 28006, Madrid, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain. Electronic address: rojodelolmo@ictp.csic.es.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2021 Feb 15; Vol. 212, pp. 113152. Date of Electronic Publication: 2021 Jan 05.
DOI: 10.1016/j.ejmech.2021.113152
Abstrakt: The 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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