Title (srp)

Ispitivanje antimikrobne i antioksidativne aktivnosti paladijum(II) kompleksa

Author

Raković, Ivana, 1983-

Contributor

Čanović, Predrag, 1959-
Radojević, Ivana, 1973-
Stanković, Slaviša, 1965-
Milošević-Đorđević, Olivera, 1963-
Bogojevski, Jovana, 1979-
Popovska Jovičić, Biljana

Description (eng)

Introduction: The main goal of the doctoral dissertation was the synthesis of the palladium(II)complexes with different nitrogen and selenium donor ligands and examining theirantimicrobial, antibiotic, and antioxidant activities, interactions with DNA molecules,genotoxic and antitumor activity. In an era of microbial resistance, the research cited was aimedat finding an antimicrobial drug with a wider range of effects that would have minimal sideeffects. It is also of medical importance to find a potential antitumor drug.Materials and methods: Standard analytical methods show the synthesis and characterizationof 7 Pd(II) complexes with different nitrogen and selenium donor ligands. Antimicrobialactivity was tested by a microdilution method with resazurin, and antibiofilm activity was testedon the formed biofilm, a method with crystal violet. A wide range of microorganisms (Grampositive, Gram-negative bacteria, yeasts, filamentous fungi) were used, ensuring that standardsand isolates were equally represented, especially pathogens. A test of the capacity to neutralizeDPPH radicals was used to test antioxidant activity. Interactions of synthesized complexes withCT-DNA were examined using the absorption and fluorescent method as well as measuring theviscosity of the solution, while interactions with BSA were examined using a fluorescentmethod. A simulation of the docking molecules was performed. The genotoxic activity ofcomplexes Pd(II) in cultivated human lymphocytes was tested using Komet tests. Cytotoxicactivity of newly synthesized compounds was tested using an MTT colourimetric technique.Results: Tested nitrogen donor ligands and corresponding Pd(II) complexes showed selectiveand limited antimicrobial activity. Complexes Pd(II) with selenium donor ligands, C5 and C7showed the most significant activity towards the bacterium Pseudomonas aeruginosa, whereactivities were better than the positive control. Activities better or in the rank of positivecontrols are shown in the case of C5 complex, on the filamentous fungus Trichoderma viridaeATCC 13233 and the species of Aspergillus, as well as in the case of the C7 complex on thebiofilm P. aeruginosa. Significant antioxidant activity of the Pd(II) complexes with nitrogendonor ligands exhibits only C4, while the C6 complex of the Pd(II) complexes with seleniumdonor ligands is significantly highlighted. The examined Pd(II) complexes moderately interactwith the CT-DNA and BSA molecules, with a slightly higher affinity towards the BSAmolecule. Selenium donor Pd(II) complexes showed greater interaction than nitrogen donorPd(II) complexes. "Minor groove" and intercalculation are equally represented as ways of binding to the CT-DNA molecule. The biggest genotoxic effect shows the C7 complex and thesmallest C5. C6 complex demonstrated the most significant antitumor activity.Conclusion: At a time of growth of microbial resistance and rates of malignant diseases,finding a potential drug with few side effects and a wide range of effects is the goal of numerousresearch groups around the world. This in vitro research singles out complex C5 as the leastgenotoxic, with a distinct antimicrobial activity towards certain microorganisms, and complexC6 with distinctive antioxidant and cytotoxic activity. Consequently, research for bothcomplexes is justified and encourages continued research in the field of the application of metalcomplexes as medicines.Keywords: Pd(II) complexes, nitrogen and selenium donor ligands, antimicrobial, antibiofilm,antioxidant activity, CT-DNA and BSA, genotoxic, cytotoxic activity

Description (srp)

Uvod: Osnovni cilj doktorske disertacije je bio sinteza kompleksa paladijuma(II) sarazličitim azot i selen donorskim ligandima i ispitivanje njihove antimikrobne,antibiofilm, antioksidativne aktivnosti, interakcije sa molekulom DNK,genotoksična i antitumorska aktivnost. U eri mikrobne rezistencije, navedenaistraživanja su imala za cilj pronalaženje antimikrobnog leka sa širim spektromdelovanja koji će imati minimum neželjenih efekata. Od medicinskog značaja je ipronalaženje potencijalnog antitumorskog leka.Materijal i metode: Prikazana je sinteza i karakterizacija 7 kompleksa Pd(II) sarazličitim azot i selen donorskim ligandima, standardnim analitičkim metodama.Antimikrobna aktivnost je ispitivana mikrodilucionom metodom sa resazurinom, aantibiofilm aktivnost na formiranom biofilmu, metodom sa kristal violetom.Korišćen je širok spektar različitih mikroorganizama (Gram-pozitivne, Gramnegativne bakterije, kvasci, filamentozne gljive), pri čemu se vodilo računa da supodjednako zastupljeni standardi i izolati, naročito patogeni. Za ispitivanjeantioksidativne aktivnosti korišćen je test kapaciteta neutralisanja DPPH radikala.Interakcije nagrađenih kompleksa sa CT-DNK praćene su apsorbcionom ifluorescentnom metodom kao i merenjem viskoznosti rastvora, dok su interakcije saBSA ispitivane fluoroscentnom metodom. Izvršena je simulacija molekula dokingmetodom. Genotoksična aktivnost kompleksa Pd(II) u kultivisanim humanimlimfocitima ispitivana je korišćenjem Komet testa. Citotoksična aktivnostnovosintetisanih jedinjenja je ispitivana pomoću MTT kolorimetrijske tehnike.Rezultati: Testirani azot-donorski ligandi i odgovarajući kompleksi Pd(II) pokazalisu selektivnu i ograničenu antimikrobnu aktivnost. Kompleksi Pd(II) sa selendonorskim ligandima, C5 i C7 pokazali su najznačajniju aktivnost prema bakterijiPseudomonas aeruginosa, pri čemu su aktivnosti bile bolje u odnosu na pozitivnukontrolu. Aktivnosti bolje ili u rangu pozitivnih kontrola pokazuje i kompleks C5,na filamentoznim gljivama Trichoderma viridae ATCC 13233 i vrstama roda Aspergillus,kao i kompleks C7 na biofilmu P. aeruginosa. Značajnu antioksidativnu aktivnostPd(II) kompleksa sa azot-donorskim liganadima pokazuje samo S4, dok se od kompleksaPd(II) sa selen donorskim ligandima značajno ističe C6 kompleks. Ispitivani kompleksi Pd(II) umereno interaguju sa molekulom CT-DNK i BSA, neštoveći afinitet pokazuju prema molekulu BSA. Selen donorski kompleksi Pd(II) supokazali veći stepen interakcije u odnosu na azot donorske komplekse Pd(II).Podjednako su zastupljeni „minor groov“ i interkalacija kao načini vezivanja samolekulom CT-DNK. Najveći genotoksični efekat pokazuje kompleks S7, a najmanji S5.Kompleks C6 je pokazao najznačajniju antitumorsku aktivnost.Zaključak: U vremenu rasta mikrobne rezistencije i stope oboljevanja od malignihbolesti, pronalazak potencijalnog leka sa malo sporednih efekata i širokog spektradejstva je cilj brojnih istraživačkih grupa širom sveta. Ovo in vitro istraživanjeizdvaja kompleks S5 kao najmanje genotoksičan, sa izrazitom antimikrobnomaktivnošću prema određenim mikroorganizmima, i kompleks S6 sa izrazitomantioksidativnom i citotoksičnom aktivnošću. Shodno tome, istraživanja za obakompleksa su opravdana i podstiču nastavak istraživanja u oblasti primene kompleksametala kao lekova.

Description (srp)

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Object languages

Serbian

Date

2021

Rights

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