Synthesis, characterization, DNA interactions and antiproliferative activity on glioblastoma of iminopyridine platinum(II) chelate complexes

• Published in: Journal of inorganic biochemistry Vol. 168; pp. 46 - 54
• Main Authors: Posadas, Inmaculada, Alonso-Moreno, Carlos, Bravo, Iván, Carrillo-Hermosilla, Fernando, Garzón, Andrés, Villaseca, Noemí, López-Solera, Isabel, Albaladejo, José, Ceña, Valentín
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cisplatin derivatives; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; DNA - chemistry; DNA-binding; Glioblastoma; Glioblastoma - drug therapy; Imines - chemistry; Imines - pharmacology; Molecular Structure; Platinum - chemistry; Platinum - pharmacology; Pyridines - chemistry; Pyridines - pharmacology; Rats; Cisplatin derivatives; DNA-binding; Glioblastoma
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2016.11.032

A series of iminopyridine platinum chelate compounds has been prepared and characterized by NMR spectroscopy and single-crystal X-ray diffraction. The complexes were evaluated in C6 tumoral cells as an in vitro model for glioblastoma multiforme. The DNA-binding properties of these complexes were studied by UV–Vis absorption and fluorescence spectroscopy and Density Functional Theory calculations were performed in an effort to rationalize the observed properties at the molecular level. The most promising drug candidate displayed a similar potency in inducing cell death to the clinically used reference compound and showed significant inhibition of glioblastoma cell proliferation. Moreover, this compound had a safer profile than cisplatin on non-tumoral cells. Iminopyridine platinum chelate compounds were screened against glioblatoma multiforme. Some of the compounds displayed an interesting antitumoral profile, with a higher potency than the standard drug Temozolamide (TMZ) in reducing glioblastoma cell proliferation. DNA interactions studies helped to shed light on the mechanism of action, which could facilitate new drug designs. [Display omitted] •The new complexes display a very interesting profile for the treatment of glioblastoma.•The cytotoxicity is due to cellular events associated with their ability to crosslink DNA.•A correlation found between the calculated free energy for hydrolysis and the cytotoxicity.