Sinteza, karakterizacija i ispitivanje biološke aktivnosti kompleksa bakra(II) sa S,O-tetradentatnim ligandima, derivatima tiosalicilne kiseline
Synthesis, characterization and examination of biological activity of copper(II) complexes with S,O-tetradentate ligands, derivatives of thiosalicylic acid
Докторанд
Živanović, Ana S.Ментор
Bukonjić, AndrianaЧланови комисије
Radić, GordanaPoljarević, Jelena
Mijajlović, Marina
Метаподаци
Приказ свих података о дисертацијиСажетак
Uvod: Terapijska primena kompleksa bakra(II) privlači pažnju istraživača zbog
mogućnosti koordinovanja sa različitim donorskim atomima. Među liganadima koji u
strukturi sadrže sumpor i kiseonik izdvaja se tiosalicilna kiselina, čiji derivati
pokazuju citotoksičnost u terapiji tumora.
Materijal i metode: U ovoj Doktorskoj disertaciji opisani su sinteza S,O
tetradentatnih liganada, derivata tiosalicilne kiseline i kompleksa bakra(II) sa
navedenim ligandima. Radi potvrde njihove strukture, sprovedena su različita merenja:
mikroanaliza, infracrvena spektroskopija, nuklearno-magnetno-rezonanciona
spektroskopija, elektronska paramagnetna rezonancija i molarna provodljivost. U
cilju procene biološke aktivnosti sprovedene su nukleofilne supstitucione
reakcije kompleksa sa endogenim ligandima (L-metioninom, L-cisteinom i 5’-GMP), in
vitro interakcije sa ST-DNK (eng. calf thymus, DNK timusa govečeta) i humanim
serumskim albuminom (HSA) pomoću apsorpcione spektroskopske analize i emisione
fluores...cencije, in silico interakcije sa DNK i HSA. Takođe, primenom MTT
kolorimetrijskog testa analizirana je citotoksičnost sintetisanih liganada i
kompleksa na tri ćelijske linije.
Rezultati: Analizom sprovedenih merenja pretpostavljena je oktaedarska
geometrija kompleksa. Svi kompleksi podležu reakcijama nukleofilne supstitucije.
Visoke vrednosti konstante vezivanja pokazuju da kompleksi interaguju sa molekulom
DNK i HSA. Interakcija sa DNK molekulom dešava se interkalacijom ili
interakcijom sa malim žlebom. Kompleksi imaju citotoksični potencijal, dok je prema
svim ćelijskim linijama najbolju citotoksičnost na osnovu IC50 vrednosti pokazao
kompleks [Cu(S,O-pentilen-tiosalicilna kiselina)].
Introduction: The therapeutic application of copper(II)-complexes attracts the
attention of researchers due to the possibility of coordination with different donor atoms.
Among the ligands that contain sulfur and oxygen in the structure, thiosalicylic acid stands out,
whose derivatives show cytotoxicity in tumor therapy.
Material and methods: In this Doctoral dissertation, the synthesis of S,O-tetradentate
ligands, derivatives of thiosalicylic acid and copper(II)-complexes with the mentioned ligands
is described. In order to confirm their structure, various measurements were performed:
microanalysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, electronic
paramagnetic resonance and molar conductivity. In order to assess biological activity,
nucleophilic substitution reactions of complexes with endogenous ligands (L-methionine, Lcysteine and 5'-GMP), in vitro interactions with ct-DNA (calf thymus DNA) and human serum
albumin (HSA) were performed by absorption spectros...copic analysis and emission
fluorescence, in silico interactions with DNA and HSA. Also, the cytotoxicity of synthesized
ligands and complexes on three cell lines was analyzed using MTT colorimetric test.
Results: The octahedral geometry of the complex was assumed by the analysis of the
performed measurements. All complexes react to nucleophiles. High values of the binding
constant indicate that the complexes interact with the DNA molecule and HSA. Interaction with
a DNA molecule occurs by intercalation or interaction with a small groove. The complexes
have cytotoxic potential, while the [Cu (S,O-pentylene-thiosalicylic acid)] complex showed the
best cytotoxicity based on IC50 values according to all cell lines.
Keywords: S,O-tetradentate ligands, copper(II) complexes, interactions, molecular
docking, antitumor activity