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Synthesis, characterization and examination of the biological activity of binuclear complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid

dc.contributor.advisorRadić, Gordana P.
dc.contributor.otherArsenijević, Nebojša N.
dc.contributor.otherSabo, Tibor J.
dc.contributor.otherJevtić, Verica V.
dc.contributor.otherBogojeski, Jovana V.
dc.creatorTomović, Dušan Lj.
dc.date.accessioned2019-03-25T12:54:44Z
dc.date.available2019-03-25T12:54:44Z
dc.date.available2020-07-03T15:15:44Z
dc.date.issued2018-11-20
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=6558
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/10951
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1072/bdef:Content/download
dc.description.abstractUvod: U ovoj Doktorskoj disertaciji ispitivane su kinetička, antimikrobna i antitumorska aktivnost novosintetisanih binuklearnih kompleksa bakra(II) sa S-alkenil derivatima tiosalicilne kiseline. Istraživanja u ovoj oblasti su fokusirana na pronalaženje biološki aktivnih kompleksnih jedinjenja. Tiosalicilna kiselina i njeni derivati su veoma interesantni kao ligandi, jer pokazuju veliku raznolikost u mogućnostima za koordinovanje. Materijal i metode: U okviru ovog istraživanja opisani su postupci sinteze Salkenil derivata tiosalicilne kiseline (alkenil = propenil- i izobutenil-) i odgovarajućih binuklearnih kompleksa bakra(II). Sastav nagrađenih jedinjenja potvrđen je na osnovu rezultata elementalne mikroanalize. Struktura sintetisanih bidentatnih liganada okarakterisana je na osnovu rezultata infracrvene (IR) i nuklearno-magnetno-rezonancione spektroskopije (1H i 13C NMR), dok je struktura odgovarajućih kompleksa pretpostavljena na osnovu rezultata infracrvene (IR) spektroskopije, magnetnih merenja i molarne provodljivosti. Stvarna struktura sintetisanog kompleksa bakra(II), predviđena je na osnovu rezultata rendgenske strukturne analize. Antimikrobna aktivnost je ispitivana mikrodilucionom metodom sa resazurinom. Supstitucione reakcije su praćene u prisustvu guanozin-5’- -monofosfata, kao i CT-DNK (DNK iz timusa govečeta). Citotoksična aktivnost novosintetisanih jedinjenja je ispitivana pomoću MTT kolorimetrijske tehnike. Rezultati: Potvrđena je stvarna struktura binuklearnog kompleksa bakra(II) sa S-izobutenil derivatom tiosalicilne kiseline. Među Gram-pozitivnim bakterijama, Staphylococcus aureus ATCC® 25923 je pokazao najveću otpornost, dok je najosetljiviji bio Bifidobacterium animalis subsp. lactis. Kompleksi bakra(II) pokazali su nisku antifungalnu aktivnost. Reakcije supstitucije ispitivanih kompleksa bile su veoma brze, a pokazano je da mogu interagovati sa ST-DNK. Bakar(II)-kompleksi su pokazali neznatno nižu citotoksičnost u poređenju sa cisplatinom. Njihov citotoksični efekat pri koncentracijama od 250 do 1000 μM na HCT-116 ćelije je kao efekat cisplatine. Zaključak: Otkriće kompleksa bakra(II) sa antimikrobnom i antitumorskom aktivnošću može bitno podstaći dalja istraživanja u oblasti koordinovanja bakar(II)-jona sa ligandima od farmakološkog značaja, koji će imati širi spektar dejstva u medicinskoj primeni sa prihvatljivim krajnjim ishodom lečenja.sr
dc.description.abstractIntroduction: This PhD thesis covers the examination of the kinetic, antimicrobial and anticancer activities of the newly synthesized binuclear complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid. Researches in this area are focused on finding biologically active complex compounds. Thiosalicylic acid and its derivatives are very interesting as ligands because they manifest a great diversity in coordination possibilities. Materials and methods: This study described the methods for the synthesis of the S-alkenyl derivatives of thiosalicylic acid (alkenyl = propenyl- and isobutenyl-) and the corresponding binuclear complexes of copper(II). The composition of the obtained compounds was confirmed by the results of the elemental microanalysis. The structure of synthesized bidentate ligands was characterized by the results of infrared (IR) and nuclear-magnetic-resonance spectroscopy (1H and 13C NMR), while the structure of the corresponding complexes was assumed by the results of infrared (IR) spectroscopy, magnetic measurements and molar conductivity. The real structure of the synthesized complex copper(II) was predicted by the results of the X-ray structural analysis. Тhe antimicrobial activity was examined by the microdilution method with resazurin. The substitution reactions were monitored in the presence of guanosine-5'-monophosphate, as well as CT-DNА (calf thymus DNA). The cytotoxic activity of the newly obtained compounds was examined by MTT colorimetric technique. Results: The real structure of the binuclear complex of copper(II) with S-isobutenyl derivative of thiosalicylic acid was confirmed. Among Gram-positive bacteria, Staphylococcus aureus ATCC® 25923 manifested the highest resistance, while Bifidobacterium animalis subsp. lactis was the most sensitive one. Copper(II)-complexes manifested a low antifungal activity. Substitution reactions of the tested complexes were very fast, and it was shown that they could interact with СT-DNA. Copper(II)-complexes displayed slightly lower cytotoxicity compared to cisplatin. Copper(II)-complexes with S-alkenyl derivatives of thiosalicylic acid (for concentrations from 250 to 1000 μM) had cytotoxic effect on HCT-116 cells as cisplatin. Conclusion: The discovery of the copper(II)-complexes with antimicrobial and anticancer activity can significantly stimulate further research in the field of copper(II) coordination with ligands of pharmacological significance, which will have a wider spectrum of effects in medical applications with the acceptable final outcome of a treatment.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41010/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172016/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectS-alkenil derivati tiosalicilne kiselinesr
dc.subjectS-alkenyl derivatives of thiosalicylic aciden
dc.subjectbinuclear copper(II)-complexesen
dc.subjectcrystal structureen
dc.subjectbiological activityen
dc.subjectbinuklearni kompleksi bakra(II)sr
dc.subjectkristalna strukturasr
dc.subjectbiološka aktivnostsr
dc.titleSinteza, karakterizacija i ispitivanje biološke aktivnosti binuklearnih kompleksa bakra(II) sa S-alkenil derivatima tiosalicilne kiselinesr
dc.title.alternativeSynthesis, characterization and examination of the biological activity of binuclear complexes of copper(II) with S-alkenyl derivatives of thiosalicylic aciden
dc.typedoctoralThesis
dc.rights.licenseBY-NC-SA
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48739/Dusan_Tomovic_Medicinski.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48738/Disertacija.pdf


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