Synthesis, characterization and potentional antitumor effects of 1,5-naphtyridine dinuclear complexes of paladaium (II)

[M. M. Bošković]

60 listova

Uvod: Ranija ispitivanja brojnih naftiridinskih derivata ukazuju na postojanje njihovog antitumorskog, antimikrobnog i antiinflamatornog dejstva. Cilj: Cilj istraživanja je bio da se ispita potencijalno antitumorsko delovanje novosintetisanih 1,5-naftiridinskih dinuklearnih kompleksa paladijuma(II). Materijal i metod: Studija je realizovana kao eksperimentalno in vitro istraživanje na nekoliko malignih ćelijskih linija. Dinuklearni kompleksi dobijeni su po modifikovanom postupku za sintezu. Karakterizacija kompleksa je izvršena primenom elementalne mikroanalize, ultraljubičaste i infracrvene spektrofotometrije, kao i pomoću nuklearno-magnetno-rezonancione spektroskopije. Vijabilnost malignih ćelija tretiranih novosintetisanim kompleksima paladijuma(II) ispitivana je MTT kolorimetrijskim testom. Analiza apoptotoze uključila je ekspresiju proapoptotskih i antiapoptotskih preoteina, koji su ispitivani protočnom citometrijom. Rezultati: Pet dinuklearnih kompleksa Pd1-Pd5 su sintetisani i spektroskopski okarakterisani. Citotoksična aktivnost je testirana na nekoliko ćelijskih linija karcinoma miša i na humanim ćelijskim linijama. Zaključak: Svi testirani Pd(II) kompleksi su smanjili održivost ćelijskih linija tumora u odnosu na datu dozu. Najviši citotoksični kapacitet pokazao je kompleks Pd5. Mogući mehanizam citotoksične aktivnosti Pd5 kompleksa je povećavanje apoptoze, kroz smanjivanje dejstva Bcl-2 i povećavanje dejstva kaspaze tip 3.

Introduction: Earlier studies of numerous naphthyridine derivatives indicates the presence of their antitumor, antimicrobial and anti-inflammatory effects. Objective: The objective of this study was to investigate the potential antitumor effect of newly synthesized 1,5-naphthyridine dinuclear palladium(II) complexes. Material and method: The study was conducted as an experimental in vitro study on several malignant cell lines. Dinuclear complexes were obtained by a modified procedure. Characterization of the complexes was carried out using elemental microanalysis, ultraviolet and infrared spectrophotometry and nuclear-magnetic-resonance spectroscopy. The viability of malignant cells treated with newly synthesized palladium(II) complexes was investigated by MTT colorimetric test. Analysis of apoptotic death involved the expression of proapoptotic and antiapoptotic proteins measured by flow cytometry. Results: Five dinuclear Pd1-Pd5 complexes were synthesized and spectroscopically characterized. Cytotoxic effect of complexes was tested on several mouse and human cancer cell lines. Conclusion: All tested Pd(II) complexes reduced the viability of tumor cell lines in correlation with the given dose. The highest cytotoxic activity was shown by the Pd5 complex. A possible mechanism of the cytotoxic effect of Pd5 complex may be increasing the apoptotic process, throw decreased activity of Bcl-2 and increased activity of caspase-3.

sinteza, karakterizacija, antitumorski efekat, 1,5-naftiridinski dinuklearni kompleks paladijuma(II)

synthesis, characterization, antitumor effect, 1,5-naphtyridine dinuclear complexes of palladium.

546.96:616-006(043.3)

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