Metal-Based Molecular Compounds: Structure, Analytical Properties, dsDNA Binding Studies and In Vitro Antiproliferative Activity on Selected Cancer Cell Lines

Development of Methotrexate Complexes Endowed with New Biological Properties Envisioned for Musculoskeletal Regeneration in Rheumatoid Arthritis Environments

“…In any case, in all these previous reports, coordination between the cations and MTX occurred exclusively over the free carboxyl groups of MTX as demonstrated by crystallographic analysis, FTIR, and/or NMR spectroscopies [ 10 , 19 , 21 , 22 , 23 ]. In our case, the analysis of the ATR–FTIR spectra revealed, as expected, that the band corresponding to υ(COOH) vibration in the MTX spectrum, located at 1682 cm −1 , did not appear in the spectra of the MTX derivatives, meaning that the metals were coordinated over the free carboxyl groups of MTX in all the cases ( Figure 4 ).…”

“…Prior to this work, there were only a few articles about metal-based derivatives of MTX. Two of them just focused on the physicochemical characterization of the reported complexes (with strontium and zinc) [ 21 , 22 ], while in two other works the authors first reported some anti-proliferation studies as well as the characterization of the complexes (bearing zinc, copper, and platinum), and then they employed the complexes as model drugs to be released from alginate-carboxymethyl cellulose composite beads [ 23 , 24 ]. Thus, this is the first time that metal-containing MTX derivatives are studied in the context of an autoimmune disease, seeking pro-regenerative effects, and this work encompasses the most in-depth biological characterization carried out so far with this kind of complexes.…”

“…On the other hand, the procedures carried out by Nodiţi et al and Çeşme et al to synthesize complexes of MTX with Zn 2+ were more similar to the one followed here, except for the ratio of ZnCl 2 to MTX that was 1:2 and 1:1, respectively, while an excess of ZnCl 2 (3:1) was added in our case. These procedures resulted in complexes where one zinc ion was coordinated by two and one MTX molecules, respectively [ 22 , 23 ].…”

“…In this framework, there are some published papers reporting the synthesis and physicochemical characterization of complexes of MTX with bioactive cations such as Sr, Zn, Cu, or Pt [ 21 , 22 , 23 , 24 ]. Exceptionally, in two of these works the authors addressed some anti-proliferation studies and loaded them into a controlled delivery system [ 23 , 24 ].…”

“…In this framework, there are some published papers reporting the synthesis and physicochemical characterization of complexes of MTX with bioactive cations such as Sr, Zn, Cu, or Pt [ 21 , 22 , 23 , 24 ]. Exceptionally, in two of these works the authors addressed some anti-proliferation studies and loaded them into a controlled delivery system [ 23 , 24 ]. Consequently, the additional positive effects of MTX complexes coming from the bioactive cation have not been explored yet and research on this topic is required prior to their final biomedical application.…”