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dc.contributor.advisorŠmelcerović, Andrija
dc.contributor.otherKocić, Gordana
dc.contributor.otherAgbaba, Danica
dc.contributor.otherMilić, Nataša
dc.contributor.otherTasić-Kostov, Marija
dc.creatorKolarević, Ana N.
dc.date.accessioned2020-02-24T11:51:30Z
dc.date.available2020-02-24T11:51:30Z
dc.date.available2020-07-03T16:09:09Z
dc.date.issued2019-07-01
dc.identifier.urihttp://eteze.ni.ac.rs/application/showtheses?thesesId=7163
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/11975
dc.identifier.urihttps://fedorani.ni.ac.rs/fedora/get/o:1605/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70052&RID=1026399725
dc.description.abstractIn this doctoral dissertation the inhibition of deoxyribonuclease I by the derivatives of thiazolidine, benzimidazole, 4H-chromene and 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine was evaluated in vitro. As a result, 23 compounds, out of 91 tested, inhibited DNase I with IC50 values below 200 μM, including ten thiazolidine, four benzimidazole, one 4H-chromene, and eight 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. These compounds were more effective DNase I inhibitors than crystal violet (IC50 > 300 μM), used as a positive control. According to the Lineweaver-Burk plots, some of the most effective DNase I inhibitors show non-competitive type of inhibition. The intermolecular interactions of the tested compounds with DNase I were predicted by molecular docking studies. To provide a more complete picture of possible therapeutic applications of the investigated thiazolidines, benzimidazoles, 4H-chromenes and 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines that inhibited DNase I with IC50 values below 200 μM, in silico study of their physico-chemical, biopharmaceutical, pharmacokinetic, and toxicological properties was performed. Most DNase I inhibitors fulfilled Lipinski’s and Veber’s rules predicting good oral bioavailability in in vitro/in vivo conditions. All compounds were predicted as able to be absorbed by intestine, as well as permeable across blood-brain barrier. Most of the tested derivatives could be preliminary classified as biopharmaceutical class I and/or II. The investigated DNase I inhibitors are generally predicted as slightly toxic and non-carcinogenic compounds, without risk of mutagenic, tumorigenic and/or irritant effects. The general conclusion of this doctoral dissertation is that the most effective DNase I inhibitors from the groups of the investigated thiazolidines, benzimidazoles, 4H-chromenes and 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines represent a good basis for the development of novel and more efficient DNase I inhibitors with potential therapeutic applications, considering the importance of DNase I in the pathophysiology of numerous disease conditions. Since there is no DNase I inhibitor defined as a "gold standard", the tested compounds could represent a new ones in future research.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Нишу, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172044/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Нишуsr
dc.subjectDezoksiribonukleaza Isr
dc.subjectDeoxyribonuclease Ien
dc.subjectInhibitionen
dc.subjectThiazolidinesen
dc.subjectBenzimidazolesen
dc.subject4H-Chromenesen
dc.subject5en
dc.subject6en
dc.subject7en
dc.subject8-Tetrahydrobenzo[4en
dc.subject5]thieno[2en
dc.subject3-d]pyrimidinesen
dc.subjectIn silico studyen
dc.subjectInhibicijasr
dc.subjectTiazolidinisr
dc.subjectBenzimidazolisr
dc.subject4H-Hromenisr
dc.subject5sr
dc.subject6sr
dc.subject7sr
dc.subject8-Tetrahidrobenzo[4sr
dc.subject5]tieno[2sr
dc.subject3-d]pirimidinisr
dc.subjectIn silico studijasr
dc.titleInhibicija dezoksiribonukleaze I derivatima tiazolidina, benzimidazola, 4H- hromena i 5,6,7,8-tetrahidrobenzo[4,5] tieno[2,3-d]pirimidina u in vitro uslovimaen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/53810/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/53811/Kolarevic_Ana_N.pdf


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