Title (srp)

Antitumorska aktivnost binuklearnih kompleksa bakra (II) sa S-izoalkil derivatima tiosalicilne kiseline

Author

Dimitrijević, Jelena D., 1978-

Contributor

Milovanović, Marija, 1979-
Pantić, Jelena, 1977-
Arsenijević, Nebojša, 1958-
Radić, Gordana, 1980-
Maksimović-Ivanić, Danijela, 1972-

Description (srp)

Brojni neželjeni efekti terapije tumora lekovima koji sadrže platinu uslovili sudizajniranje novih potencijalnih terapeutika u kojima je platina zamenjena drugimprelaznim metalom. Bakar se zahvaljujući aktivnim sistemima transporta u većojkoncentraciji nalazi u tumorskim nego u zdravim ćelijama, pa postoji mogućnost dakompleksi bakra sa odgovarajućim ligandom imaju selektivniju citotoksičnost, štoje uticalo na razvoj različitih serija kompleksa bakra u cilju pronalaženjapotencijalnog selektivnijeg hemoterapeutika. Cilj ove studije je karakterizacijasintetisanih binuklearnih kompleksa bakra(II) sa S-izoalkil derivatimatiosalicilne kiseline i analiza antitumorskog efekta sintetisanih kompleksa.Kompleksi su sintetisani, a njihova struktura je opisana na osnovu elementalnemikroanalize i potvrđena na osnovu infracrvene i nuklearno-magnetno-rezonancionespektroskopije i rendgenske strukturne analize. Binuklearni kompleksi bakra(II) saS-izoalkil derivatima tiosalicilne kiseline pokazuju citotoksički efekat naćelijama mišjeg karcinoma kolona i pluća, kao i humanog kolorektalnog iadenokarcinoma pluća in vitro, indukuju apoptozu ćelija mišjeg Lewis karcinoma plućai zaustavljaju tumorske ćelije u G2/M fazi ćelijskog ciklusa. Binuklearni kompleksbakra(II) sa S-izoamil derivatom tiosalicilne kiseline značajno smanjuje ekspresijuinflamacijskih molekula, pro-IL-1β, TNF-α, ICAM-1 i VCAM-1, u tkivu primarnogheterotopskog mišjeg karcinoma kolona što je praćeno značajnom redukcijom rastatumora kao i smanjenjem incidence, veličine i broja metastaza u plućima i jetri.Rezultati ove studije ukazuju da binuklearni kompleks bakra(II) sa S-izoamilderivatom tiosalicilne kiseline, pokazuju antitumorski efekat in vitro, kao iznačajan efekat in vivo u modelu karcinoma kolona miša.

Description (srp)

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Description (eng)

Numerous side effects of platinum based chemotherapy caused the design of new therapeuticswith platinum replaced by another transition metal. Concentration of copper is higher incancer than in normal cells implying the possibility that copper complexes with theappropriate ligand could have more selective cytotoxicity. This led to the development ofdifferent series of copper complexes in order to find a potential more selectivechemotherapeutics. The aim of this study is to characterize the synthesized binuclearcomplexes of copper(II) with S-isoalkyl derivatives of thiosalicylic acid and to analyze theirantitumor effect. The complexes were synthesized, and their structure was described on thebasis of elemental microanalysis, confirmed on the basis of infrared and nuclear-magneticresonance spectroscopy and X-ray structural analysis. Binuclear complexes of copper(II) withS-isoalkyl derivatives of thiosalicylic acid show a cytotoxic effect on mouse colon lungcarcinoma cells, as well as human colorectal and lung adenocarcinoma cells in vitro, induceapoptosis of mouse lung carcinoma cells and arrest tumor cells in G2/M phase of the cellcycle. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acidsignificantly reduces the expression of inflammatory molecules, pro-IL-1β, TNF-α, ICAM-1and VCAM-1, in tissue of primary heterotopic murine colon cancer, which is accompanied bya significantly reduced tumor growth and the incidence, size and number of lung and livermetastases.The results of this study indicate that the dinuclear complex of copper(II) with the S-isoamylderivative of thiosalicylic acid, exert the antitumor effect in vitro, as well as significantantitumor effect in vivo in the model of mouse heterotopic primary colon cancer.

Object languages

Serbian

Date

2023

Rights

Creative Commons License
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CC BY-NC-ND 3.0 AT - Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Identifiers