Synthesis and In Vitro Studies of Photoactivatable Semisquarainetype Pt(II) Complexes
Metadatos
Mostrar el registro completo del ítemEditorial
American Chemical Society
Fecha
2022-05-06Referencia bibliográfica
Inorg. Chem. 2022, 61, 7729−7745. [https://doi.org/10.1021/acs.inorgchem.1c03957]
Patrocinador
Instituto de Salud Carlos III; Spanish Government RTI2018-098027-B-C22; European Commission BIO2015-67358-C2-2-P CTQ2016-75363-R; Spanish Government Instituto de Salud Carlos III Spanish Government; Generalitat de Catalunya 2017SGR-864Resumen
The synthesis, full characterization, photochemical
properties, and cytotoxic activity toward cisplatin-resistant cancer
cell lines of new semisquaraine-type Pt(II) complexes are
presented. The synthesis of eight semisquaraine-type ligands has
been carried out by means of an innovative, straightforward
methodology. A thorough structural NMR and X-ray diffraction
analysis of the new ligands and complexes has been done. Density
functional theory calculations have allowed to assign the trans
configuration of the platinum center. Through the structural
modification of the ligands, it has been possible to synthesize some
complexes, which have turned out to be photoactive at
wavelengths that allow their activation in cell cultures and,
importantly, two of them show remarkable solubility in biological
media. Photodegradation processes have been studied in depth, including the structural identification of photoproducts, thus
justifying the changes observed after irradiation. From biological assessment, complexes C7 and C8 have been demonstrated to
behave as promising photoactivatable compounds in the assayed cancer cell lines. Upon photoactivation, both complexes are capable
of inducing a higher cytotoxic effect on the tested cells compared with nonphotoactivated compounds. Among the observed results,
it is remarkable to note that C7 showed a PI > 50 in HeLa cells, and C8 showed a PI > 40 in A2780 cells, being also effective over
cisplatin-resistant A2780cis cells (PI = 7 and PI = 4, respectively). The mechanism of action of these complexes has been studied,
revealing that these photoactivated platinum complexes would actually present a combined mode of action, a therapeutically
potential advantage.