Naslov (srp)

Novi heteronuklearni Pt(II)-L-Zn(II) kompleksi: ispitivanje antitumorske aktivnosti na ćelijama kolorektalnog karcinoma, in vitro

Autor

Vučelj, Samir, 1982-

Doprinosi

Soldatović, Tanja, 1976-
Jovanović, Ivan, 1977-
Simović Marković, Bojana, 1984-
Stojković, Danijela, 1986-
Grgurić-Šipka, Sanja, 1971-

Opis (eng)

Introduction: A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with4,4,4-tri-tert-butyl-2,2′:6′,2″-terpyridine ligand were synthesized, and characterized.Material and methods: The DNА and protein binding properties of [ZnCl2(terpytBu)] (C1),[{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4)and [{trans-PtCl(NH3)2(μ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (terpytBu = 4,4′,4″-tritert-butyl-2,2′:6′,2″-terpyridine), were investigated by electronic absorption, fluorescencespectroscopic, and molecular docking methods. The in vitro anticancer activity of thecomplexes was investigated in murine cancer cell lines and a normal murine cell line by MTTassay.Results: Complexes featuring transplatin exhibited a lower Kb and Ksv constant valuescompared to cisplatin analogues. The lowest Ksv value belonged to complex C1, while C4exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNAis due to van der Waals forces while, that of C2-C5 is due to conventional hydrogen bonds andvan der Waals forces. The tested complexes exhibited variable cytotoxicity toward mousecolorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and noncancerousmouse mesenchymal stem cells (mMSC). Particularly, mononuclear C1 complexshowed pronounced selectivity towards cancer cells over non-cancerous mMSC. The C1complex notably induced apoptosis in CT26 cells and effectively arrested the cell cycle in theG0/G1 phase and selectively down-regulated Cyclin D.Conclusion: Obtained results indicate that these novel mono- and heteronuclear platinum(II)and zinc(II) complexes revealed activity in colorectal cancer and have the potential to becomepossible candidates for cancer treatment.

Opis (srp)

Uvod: Sintetisana je i okarakterisana serija mono- i heteronuklaeranih komleksaplatine(II) i cinka(II) sa inertnim ligandom 4,4′,4-tri-tert-butil-2,2′:6′2′′-terpiridinom.Materijal i metode: DNK i protein-vezujuća svojstva [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(μ-pirazin)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pirazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4’-bipiridil)ZnCl(terpytBu)}](CIO4)2 (C4),[{trans-PtCl(NH3)2(μ-4,4’-bipiridil)ZnCl(terpytBu)}](CIO4)2 (C5) kompleksa (gde jeterpytBu=4,4′,4-tri-tert-butil-2,2′:6′2′′-terpiridin) ispitana su putem elektronskeapsorpcije, fluorescencije i metodom molekuluskog dokinga. Antikancerogenaaktivnost kompleksa platine(II) i cinka(II) je ispitivana na ćelijskim linijamamišijeg karcinoma kolorektuma, kao i n a zdravoj liniji mezenhimalnih matičnihćelija miša, korišćenjem MTT testa.Rezultati: Kompleksi koji sadrže transplatinu pokazali su niže vrednosti konstantiKb i Ksv u poređenju sa cisplatinskim analozima. Najnižu vrednost Ksv imao je kompleksC1, dok je C4 pokazao najvišu. Molekulske doking studije su pokazale da je vezakompleksa C1 sa DNK posledica van der Valsovih sila, dok su veze C2-C5konvencionalne vodonične veze i van der Valsovih sile. Testirani kompleksi pokazalisu varijabilnu citotoksičnost prema mišjem kolorektalnom karcinomu (CT26),ljudskom kolorektalnom karcinomu (HCT116 i SW480) i normalnim mišjimmezenhimalnim matičnim ćelijama (mMSC). Posebno, mononuklearni kompleks C1pokazao je izraženu selektivnost prema kancerogenim ćelijama u odnosu nanekancerogene mMSC. Kompleks C1 značajno je izazvao apoptozu u CT26 ćelijama,efikasno zaustavio ćelijski ciklus u fazi G0/G1, i selektivno smanjio izražajciklina D.Zaključak: Dobijeni rezultati ukazuju da novosintetisani mono- i heteronukleranikomleksi platine(II) i cinka(II) pokazuju antitumorsku aktivnost na tumorskimćelijama kolorektalnog karcinoma i imaju potencijal da postanu mogući kandidati uantikancerskoj terapiji.

Opis (srp)

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Jezik

srpski

Datum

2025

Licenca

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