title: The Biginelli reaction with an imidazolium-tagged recyclable iron catalyst: kinetics, mechanism, and antitumoral activity.
abstract: The present work describes the synthesis, characterization, and application of a new ion-tagged iron catalyst. The catalyst was employed in the Biginelli reaction with impressive performance. High yields have been achieved when the reaction was carried out in imidazolium-based ionic liquids (BMI⋅PF6, BMI⋅NTf2, and BMI⋅BF4), thus showing that the ionic-liquid effects play a role in the reaction. Moreover, the ion-tagged catalyst could be recovered and reused up to eight times without any noticeable loss in activity. Mechanistic studies performed by using high-resolution electrospray-ionization quadrupole-time-of-flight mass (HR-EI-QTOF) spectrometry and kinetic experiments indicate only one reaction pathway and rule out the other two possibilities under the development conditions. The theoretical calculations are in accordance with the proposed mechanism of action of the iron catalyst. Finally, the 37 dihydropyrimidinone derivatives, products of the Biginelli reaction, had their cytotoxicity evaluated in assays against MCF-7 cancer cell linages with encouraging results of some derivatives, which were virtually non-toxic against healthy cell linages (fibroblasts).
authors: Laboratory of Medicinal and Technological Chemistry, University of Brasilia (IQ-UnB), Campus Universitário Darcy Ribeiro, CEP 70904970, P.O.Box 4478, Brasilia-DF, Brazil.
authors: Luciana M
authors: LM
authors: Ramos
authors: Bruna C
authors: BC
authors: Guido
authors: Catharine C
authors: CC
authors: Nobrega
authors: José R
authors: JR
authors: Corrêa
authors: Rafael G
authors: RG
authors: Silva
authors: Heibbe C B
authors: HC
authors: de Oliveira
authors: Alexandre F
authors: AF
authors: Gomes
authors: Fábio C
authors: FC
authors: Gozzo
authors: Brenno A D
authors: BA
authors: Neto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011744:Pyrimidinones; D007501:Iron