Title (srp)

Antitumorska i antimikrobna aktivnost novosintetisanih kompleksa platine (II) i paladijuma (II)

Author

Zornić, Sanja, 1976-

Contributor

Pantić, Jelena, 1977-
Živković, Marija, 1979-
Čobeljić, Božidar, 1983-
Simović Marković, Bojana, 1984-

Description (srp)

Kompleksi platine (Pt) i paladijuma (Pd) predstavljaju veliku grupu potencijalnihkandidata za razvoj antitumorske i antimikrobne terapije.U ovoj studiji sintetisani su dinuklearni kompleksi Pt(II) sa piridazinom kaomostnim ligandom i dinuklearni kompleksi Pd(II) sa aromatičnim N-heterocikličnimmostnim ligandima i analizirane njihove strukturne osobine i biološka aktivnost.Evaluacija tumoricidne aktivnosti kompleksa Pt(II) i Pd(II) ukazala je na varijabilancitotoksički efekat na različitim linijama tumorskih ćelija mišjeg i humanogporekla, kao i potencijalno manju toksičnost u poređenju sa cisplatinom. KompleksiPt(II) i Pd(II) su pokazali umeren antibakterijski i antigljivični efekat u zavisnostiod hemijske strukture i vrste mikroorganizma. Najveću dozno i vremenski zavisnutumoricidnu aktivnost na ćelijama mišjeg i humanog karcinoma dojke in vitro, ispoljioje kompleks [{Pt(ibn)Cl}2(-pydz)]Cl2 (gde je ibn izobutilendiamin, a pydz piridazin),označen kao S2. Kompleks S2 indukuje unutrašnji put apoptoze ćelija karcinoma dojkešto je dokumentovano povećanjem ekspresije kaspaze 9 i kaspaze 3. Antiproliferativniefekat kompleksa S2 ogleda se u smanjenju ekspresije regulatora ćelijskog ciklusaciklina E i ciklina D3 i povećanju ekspresije inhibitora r27. Proapoptotski iantiproliferativni efekat kompleksa S2 je posledica smanjene ekspresijefosforilisane protein kinaze AKT i sledstveno onkogena s-Myc. Međutim, efekatkompleksa S2 na rast mišjeg karcinoma dojke in vivo je izostao, što se može objasnitislabim vezivanjem za netransportno mesto proteina i ograničenim dopremanjem utumorsko tkivo.Validan tumoricidni i antimikrobni potencijal kompleksa Pt(II) i Pd(II) ukazuje namogućnost daljih modifikacija u cilju poboljšanja biološke aktivnosti ipotencijalne terapijske primene.

Description (srp)

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Description (eng)

Platinum (Pt) and palladium (Pd) complexes are a large group of potential candidates for thedevelopment of antitumor and antimicrobial therapy.In this study, dinuclear Pt(II) complexes with pyridazine bridging ligand and dinuclear Pd(II)complexes with aromatic N-heterocyclic bridging ligands were synthesized and their structuralproperties and biological activity were analyzed.Evaluation of Pt(II) and Pd(II) complexes tumoricidal activity indicated variable cytotoxiceffects on different mouse and human tumor cell lines, and potentially lower toxicity comparedto cisplatin. Pt(II) and Pd(II) complexes showed moderate antibacterial and antifungal effectsdepending on the chemical structure and microorganism species. Complex [{Pt(ibn)Cl}2(-pydz)]Cl2 (ibn is isobutylenediamine and pydz is pyridazine), marked as C2, exhibited thehighest dose- and time-dependent tumoricidal activity on mouse and human breast cancer cellsin vitro. Complex C2 induces the intrinsic pathway of breast cancer cells apoptosis, documentedby elevated caspase 9 and caspase 3 expression. Antiproliferative effect of complex C2 isreflected in the decreased expression of cell cycle regulators cyclin E and cyclin D3 and theincreased expression of inhibitor p27. Proapoptotic and antiproliferative effects of complex C2are consequences of reduced expression of phosphorylated AKT kinase and c-Myc oncogene.However, the effect of complex C2 on mouse breast cancer growth was absent, which can beexplained by weak binding to the non-transport site of the protein and limited delivery to tumor.The valid tumoricidal and antimicrobial potential of Pt(II) and Pd(II) complexes indicates thepossibility of further modifications in order to improve biological activity and potentialtherapeutic application.

Object languages

Serbian

Date

2024

Rights

Creative Commons License
This work is licensed under a
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