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Investigation of interactions of biologically active quinone avarone and its derivates with lysozyme, linear and circular deoxyribonucleic acid

dc.contributor.advisorSladić, Dušan
dc.contributor.otherKostić-Rajačić, Slađana
dc.contributor.otherVujčić, Zoran
dc.contributor.otherRoglić, Goran
dc.creatorNovaković, Irena T.
dc.date.accessioned2016-01-05T12:59:46Z
dc.date.available2016-01-05T12:59:46Z
dc.date.available2020-07-03T10:12:54Z
dc.date.issued2012-05-29
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/3464
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=242
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:5513/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=43574543
dc.description.abstractCilj našeg rada bio je ispitivanje biološke aktivnosti metilamino- i metoksiderivata avarona i razjašnjavanje mehanizma njihovog biološkog dejstva. Za sintezu su izabrani derivati za koje se očekivalo da će imati negativniji polutalasni potencijal od avarona i samim tim pokazivati povećanu aktivnost. Sintetisani su 4'-(metilamino)-avaron, 3'-(metilamino)-avaron i 3'-metoksi-avaron. Antibakterijska aktivnost dobijenih derivata je ispitivana prema gram-pozitivnim bakterijama: Bacillus subtilis, Clostridium sporogenes, Streptosporangium longisporum, Micrococcus flavus, Sarcina lutea i Staphylococcus aureus, prema gramnegativnim bakterijama: Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enteritidis, Escherichia coli i prema kulturama gljivica: Aspergillus niger, Candida albicans i Saccharomyces cerevisiae disk-difuzionom metodom. Takođe, ispitivana je i toksičnost derivata na račiće Artemia salina. Potencijalna antioksidativna aktivnost avarona i dobijenih derivata ispitivana je testom sa DPPH. Antitumorska aktivnost ispitivana je za sve derivate na osam vrsta ćelija raka (ćelijske linije raka grlića materice, melanoma i leukemije, rak dojke pozitivan na estrogeni receptor, rak dojke negativan na estrogeni receptor, rak pluća, leukemija T-ćelija i promijelocitna leukemija) pri čemu je ispitivana i njihova citotoksičnost na limfocite. Svim hinonskim derivatima hemijski je modifikovan model-enzim lizozim. Dobijenim modifikatima lizozima je nakon modifikacije određena enzimska aktivnost. Sama modifikacija je praćena UV/Vis spektrofotometrijom, SDS elektroforezom i masenom spektrometrijom. Mesto vezivanja hinonskih derivata za molekul lizozima određeno je tehnikom MALDI TOF posle tripsinske digestije modifikata. S obzirom na uočeno vezivanje avaronskih derivata za ε-amino grupu lizina (Lys-97) u lizozimu, sintetisano je jedinjenje 4'-((5-tert-butoksikarbonil)amino)-5-karboksipentil)amino)- avarona, koje je poslužilo kao model jedinjenje za dalja ispitivanja biološke aktivnosti lizozim-hinonskog adukta...sr
dc.description.abstractaim of our work has been investigation of biological activity of methylamino- and metoxy- derivatives of avarone, their bioconjugates of lysozyme and study of the mechanism of their biological action. For synthesis were chosen derivatives for which it was expected to have more negative half-wave potential than avarone and therefore a higher activity. The selected compounds are 3’-methylamino, 4’-methylamino- and 3’-methoxyavarone. Antimicrobial activity of the synthesized derivatives was investigated towards Gram positive bacteria: Bacilus subtilis, Clostridium sporogenes, Sreptosporangium longisporum., Micrococcus flavus, Sarcina lutea and Staphylococcus aureus, Gram negative bacteria: Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enteritidis and Escherichia coli and fungi cultures: Aspergilus niger, Candida albicans and Sacharomyces cerevisiae, all by disc diffusion method. Toxicity against Artemia salina nauplii was surveyed as well. Antioxidant activity of avarone and its derivatives was assessed by DPPH assay. Antitumor activity was determined for all derivatives towards eight lines of tumor cells (myelogenous leukemia (K562), cervix carcinoma (HeLa), human malignant melanoma cells (Fem-X), Jurkat T cell leukemia, estrogen receptor negative breast carcinoma (MDA-MB-231), estrogen receptor positive breast carcinoma (MCF7), human fetal lung fibroblast (MRC-5) and human promyelocytic leukemia (HL-60)). For all derivatives toxicity towards lymphocytes was determined. Model enzyme lysozyme was modified with the synthesized quinones and for all the obtained bioconjugates MIC value towards Gram positive and Gram negative bacteria were determined. Modification reaction was monitored by UV/VIS spectrophotometry, SDS electrophoresis and mass spectrometry. Binding position of quinone derivatives on lysozyme was determined by MALDI TOF spectrometry after trypsin digestion. Since the avarone derivatives were found to bind to lysine (Lys-97) in lysozyme, 4’-((5-((tert-butoxycarbonyl)amino)-5-carboxypentyl)-amino)avarone has been synthesized as a model compound for further investigation of the biological activity of lysozyme―quinone aduct..,en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Хемијски факултетsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectavaronsr
dc.subjectavaroneen
dc.subjectbiological activityen
dc.subjectmodificationen
dc.subjectlysozymeen
dc.subjectlinear and circular DNAen
dc.subjectbiološka aktivnostsr
dc.subjectmodifikacijasr
dc.subjectlizozimsr
dc.subjectlinearna i cirkularna DNAsr
dc.titleProučavanje interakcija biološki aktivnog hinona avarona i njegovih derivata sa lizozimom, linearnom i cirkularnom dezoksiribonukleinskom kiselinomsr
dc.titleInvestigation of interactions of biologically active quinone avarone and its derivates with lysozyme, linear and circular deoxyribonucleic aciden
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractСладић, Душан; Костић-Рајачић, Слађана; Роглић, Горан; Вујчић, Зоран; Новаковић, Ирена Т.; Проучавање интеракција биолошки активног хинона аварона и његових деривата са лизозимом, линеарном и циркуларном дезоксирибонуклеинском киселином; Проучавање интеракција биолошки активног хинона аварона и његових деривата са лизозимом, линеарном и циркуларном дезоксирибонуклеинском киселином;
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/29348/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/29348/Disertacija.pdf
dc.identifier.doi10.2298/bg20120529novakovic
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_3464


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