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Derivatives of ethylendiamine N,N'-di-2-(3-cyclohexyl) propanoic acid with potential cytotoxic activity - in silico/in vitro physicochemical and ADME characterization

dc.contributor.advisorMarković, Bojan
dc.contributor.otherVladimirov, Sote
dc.contributor.otherSabo, Tibor
dc.contributor.otherStojisavljević Šatara, Svjetlana
dc.contributor.otherDobričić, Vladimir
dc.creatorTubić, Biljana K.
dc.date.accessioned2020-09-30T14:53:48Z
dc.date.available2020-09-30T14:53:48Z
dc.date.issued2018
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=5707
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/9347
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:17453/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=49966863
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3673
dc.description.abstractEstri (S,S)-1,2-etandiamin-N,N'-di-2-(3-cikloheksil)propanske kiseline(EDCP) sa metanolom (DM-EDCP), etanolom (DE-EDCP), propanolom (DPEDCP),butanolom (DB-EDCP) i izobutanolom (DIB-EDCP) i estri (S,S)-1,3-propandiamin-N,N'-di-2-(3-cikloheksil)propanske kiseline (PDCP) sametanolom (DM-PDCP), etanolom (DE-PDCP), propanolom (DP-PDCP),butanolom (DB-PDCP), izobutanolom (DIB-PDCP), pentanolom (DPE-PDCP) iizopentanolom (DIPE-PDCP) dizajnirani su kao ligandi za Pt(IV) komplekse. Uin vitro ispitivanjima utvrđena je značajna citotoksična aktivnost za navedenekomplekse, ali i za ligande u nevezanom obliku. Ispitivana supstanca DE-EDCPpokazala je najveću citotoksičnu aktivnost.U ovoj doktorskoj disertaciji opisan je razvoj i validacija savremenebioanalitičke metode - ultra visoko efikasne tečne hromatografije u sprezi samasenom detekcijom (UHPLC-MS/MS). Metoda je razvijena i validirana zapotrebe pretkliničkih ispitivanja, odnosno za određivanje ispitivane supstanceDE-EDCP u biološkom materijalu, kao i njenog potencijalnog metabolita EDCP.Kao interni standard primenjen je strukturni analog DB-PDCP.Tokom in vitro fizičko-hemijske biofarmaceutske karakterizacije ispitivanihsupstanci određena je i ocenjena njihova rastvorljivost u vodenom rastvoru,lipofilnost i permeabilnost na veštačkim membranama. Profili rastvorljivostikiselina i njihovih estara se značajno razlikuju, dok su profili rastvorljivosti obekiseline (EDCP i PDCP) slični, kao i profili rastvorljivosti svih estara. Kiseline sedobro rastvaraju u izrazito kiseloj sredini i u izrazito baznoj sredini, dok jerastvorljivost estara najveća u izrazito kiseloj sredini...sr
dc.description.abstractEsters of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid(EDCP) with methyl alcohol (DM-EDCP), ethyl alcohol (DE-EDCP), n-propylalcohol (DP-EDCP), n-butyl-alcohol (DB-EDCP) and isobutyl-alcohol (DIBEDCP),and esters of (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP) with methyl alcohol (DM-PDCP), ethylalcchol (DE-PDCP), n-propyl alcohol (DP-PDCP), n-butyl alcohol (DB-PDCP),and isobutyl alcohol (DIB-PDCP), n-pentyl alcohol (DPE-PDCP) and isopentylalcohol (DIPE-PDCP) were designed as ligand of Pt(IV) complexes. During the invitro investigation it was found significantly cytotoxic activity of thesecomplexes, and also it was found cytotoxic activity of ligand without complexes.Investigated substance DE-EDCP was exerted the strongest cytotoxic activity.In this doctoral dissertation, there is presented a development and validationof a new ultra-high-performance liquid chromatography tandem massspectrometry bioanalytical method (UHPLC-MS/MS). The developed method issupposed for determination of DE-EDCP and its potential metabolit EDCP inbiological materials during non-clinical and clinical studies. The structuralanalogue DB-PDCP was used as an internal standard.During the in vitro biopharmaceutical characterization of the investigatedsubstances, there was performed a determination of solubility, lipophilicity andmembrane permeability. Profiles of solubility of the observed acids and theircorresponding esters are significantly different, while the profiles of solubility fortwo acids (EDCP and PDCP) are similar as well as the profiles of solubility for allthe esters...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectderivati 1sr
dc.subjectderivatives of (Sen
dc.subjectS)-1en
dc.subject2-ethanediamine-Nen
dc.subjectN'-di-2-(3-cyclohexyl)propanoic acid and (Sen
dc.subjectS)-1en
dc.subject3-propanediamine-Nen
dc.subjectN'-di-2-(3-cyclohexyl)propanoic aciden
dc.subjectbioanalytical methoden
dc.subjectultra-high performance liquidchromatography tandem mass spectrometry-UHPLC-MS/MS)en
dc.subjectsolubilityen
dc.subjectlipophilicityen
dc.subjectmembrane permeabilityen
dc.subjectdocking studyen
dc.subjectADME(T) predictionen
dc.subjectprediction of metabolic reactions and metabolites - Metabolizeren
dc.subject2-etandiamin-Nsr
dc.subjectN'-di-2-(3-cikloheksil)propanskekiselinesr
dc.subjectderivati 1sr
dc.subject3-propandiamin-Nsr
dc.subjectN'-di-2-(3-cikloheksil)propanske kiselinesr
dc.subjectbioanalitička metodasr
dc.subjecttečna hromatografija pod ultra visokim pritiskom u sprezisa masenom spektrometrijom (UHPLC-MS/MS)sr
dc.subjectrastvorljivostsr
dc.subjectlipofilnostsr
dc.subjectmembranska permeabilnostsr
dc.subjectdockingsr
dc.subjectADME(T) predviđanjesr
dc.subjectpredviđanjemetaboličkih reakcija i metabolita - Metabolizersr
dc.titleDerivati etilendiamin-N,N'-di-2-(3-cikloheksil) propanske kiseline sa potencijalnim citotoksičnim dejstvom - in silico/in vitro fizičko-hemijska i ADME karakterizacijasr
dc.title.alternativeDerivatives of ethylendiamine N,N'-di-2-(3-cyclohexyl) propanoic acid with potential cytotoxic activity - in silico/in vitro physicochemical and ADME characterizationen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractМарковић, Бојан; Сабо, Тибор; Стојисављевић Шатара, Свјетлана; Владимиров, Соте; Добричић, Владимир; Тубић, Биљана К.; Деривати етилендиамин-Н,Н'-ди-2-(3-циклохексил) пропанске киселине са потенцијалним цитотоксичним дејством - ин силицо/ин витро физичко-хемијска и AДМЕ карактеризација; Деривати етилендиамин-Н,Н'-ди-2-(3-циклохексил) пропанске киселине са потенцијалним цитотоксичним дејством - ин силицо/ин витро физичко-хемијска и AДМЕ карактеризација;
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8116/Disertacija.pdf
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8117/IzvestajKomisije16011.pdf
dc.type.versionpublishedVersion


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