Seven new Casiopeinas® were synthesized and properly characterized. These novel compounds have a general formula [Cu(N-N)(Indo)]NO3, where Indo is deprotonated indomethacin and N-N is either bipyridine or phenanthroline with some methyl-substituted derivatives, belonging to the third generation of Casiopeinas®. Spectroscopic characterization suggests a square-based pyramid geometry and voltammetry experiments indicate that the redox potential is strongly dependent on the N-N ligand. All the presented compounds show high cytotoxic efficiency, and most of them exhibit higher efficacy compared to the well-known cisplatin drug and acetylacetonate analogs of the first generation. Computational calculations show that antiproliferative behavior can be directly related to the volume of the molecules. Besides, a chitosan (CS)-polyacrylamide (PNIPAAm) nanogel was synthesized and characterized to examine the encapsulation and release properties of the [Cu(4,7-dimethyl-1,10-phenanthroline)(Indo)]NO3 compound. The results show good encapsulation performance in acidic conditions and a higher kinetic drug release in acidic media than at neutral pH. This result can be described by the Peppas-Sahlin model and indicates a release mechanism predominantly by Fick diffusion.
Bibliographical noteFunding Information:
The authors thank the projects of CONACyT Thematic Network 294727 (Farmoquímicos). Y. G. L. (grant 604136) L. F. H. A. (grant 307725). MR thanks UNAM-DGTIC for LANCAD-UNAM-DGTIC-410. The authors gratefully acknowledge Cedric Reyes Cadena, M. in C. Virginia Gomez Vidales, M. in C. Adrián Espinoza-Guillén, Dr Ernesto Rivera García for the computational and technical support to obtain EPR and SEM studies, respectively.
© 2022 The Royal Society of Chemistry.