Sinteza, karakterizacija i potencijalni antitumorski efekti mononuklearnih 5,6- epoksi-5,6-dihidro-1,10-fenantrolinskih kompleksa platine(II)
Synthesis, characteristics and potential antitumor effects of mononuclear 5,6-epoxy-5,6-dihydro-1,10- phenanthroline platinum (II) complexes
Докторанд
Dimitrijević Stojanović, MilicaМентор
Jovanović, IvanЧланови комисије
Živković, MarijaJurišević, Milena
Mitrović, Slobodanka
Čobeljić, Božidar
Метаподаци
Приказ свих података о дисертацијиСажетак
Uvod: Četiri Pt(II) kompleksa opšte formule [Pt(L)(5,6-epoxy-1,10-phen)], gde je L
anjon malonske kiseline (mal, Pt1), 2-metilmalonske kiseline (Me-mal, Pt2), 2,2-
dimetilmalonske kiseline (Me2-mal, Pt3) i 1,1-ciklobutandikarboksilne kiseline
(CBDCA, Pt4) i 5,6-epoksi-1,10-fen je 5,6-epoksi-5,6-dihidro-1,10-fenantrolin.
Materijal i metode: Kompleksi su sintetizovani i okarakterisani elementalnom
mikroanalizom i različitim spektroskopskim tehnikama. Kristalna struktura
anhidrovanog kompleksa Pt3 određena je difrakcijom rendgenskih zraka
monokristala. Antikancerogena aktivnost kompleksa platine(II) je ispitivana u
ljudskim i mišjim ćelijskim linijama karcinoma dojke i kolorektuma, kao i u
zdravoj liniji mezenhimalnihn matičnih ćelija miša, korišćenjem MTT testa.
Rezultati: Ispitivani kompleksi platine(II) pokazuju snažnu citotoksičnu
aktivnost protiv ćelija karcinoma dojke miša (4T1), humanih (HCT116) i mišjih
(CT26) ćelija kolorektalnog karcinoma. Pt3 kompleks pokazuje jaču selekt...ivnost
protiv tumorskih ćelija u poređenju sa drugim ispitivanim kompleksima platine(II)
i na taj način pokazuje korisnu antitumorsku aktivnost, uglavnom indukujući
apoptozu i inhibiciju proliferacije i migracije tumorskih ćelija. Pt3 kompleks,
takođe pokazuje značajnu in vivo antitumorsku aktivnost u ortotopskom modelu tumora
dojke, bez toksičnosti za jetru, bubrege, pluća i srce.
Zaključak: Svi rezultati ukazuju da novosintetisani kompleksi platine(II) imaju
dobru antitumorsku aktivnost na tumorske ćelije karcinoma dojke i kolorektalnog
karcinoma i imaju potencijal da postanu mogući kandidati u antikancerskoj
terapiji.
Introduction: Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)],
where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2),
2,2-dimethylmalonic acid (Me2-mal, Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4)
and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline.
Material and methods: Complexes were synthesized and characterized by elemental
microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3
complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity
of the platinum(II) complexes was investigated in human and murine cancer cell lines as well
as in a normal murine cell line by MTT assay.
Results: The results show that the investigated platinum(II) complexes exhibit potent
cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine
(CT26) colorectal carcinoma cells. The Pt3 complex shows stronger selec...tivity against cancer
cells compared to other platinum(II) complexes tested and thus exhibits beneficial antitumor
activity, mainly by inducing apoptosis and inhibiting cell proliferation and migration. The Pt3
complex also exhibits significant in vivo antitumor activity in the orthotopical 4T1 tumor
model without detected liver, kidney, lung, and heart toxicity.
Conclusion: All the results indicate that these novel platinum(II) complexes have good
antitumor activity on breast and colorectal cancer and have the potential to become possible
candidates for cancer treatment.