
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/">
  <dc:description xml:lang="eng">In 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 &gt; 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 &quot;gold standard&quot;, the tested compounds could represent a new ones in future research.</dc:description>
  <dc:description xml:lang="srp">Beleška o autoru: listovi 131-132;Bibliografija: 118-130.  Datum odbrane: 01.07.2019. Pharmaceutical sciences;Pharmaceutical chemistry and Biopharmacy.</dc:description>
  <dc:type>info:eu-repo/semantics/bachelorThesis</dc:type>
  <dc:rights>http://creativecommons.org/licenses/by-nc-nd/2.0/at/legalcode</dc:rights>
  <dc:creator>Kolarević, Ana N. 1989-</dc:creator>
  <dc:identifier>https://phaidrani.ni.ac.rs/o:1605</dc:identifier>
  <dc:identifier>cobiss:1026399725</dc:identifier>
  <dc:identifier>thesis:7163</dc:identifier>
  <dc:title xml:lang="srp">Inhibicija dezoksiribonukleaze I derivatima tiazolidina, benzimidazola, 4H- hromena i 5,6,7,8-tetrahidrobenzo[4,5] tieno[2,3-d]pirimidina u in vitro uslovima</dc:title>
  <dc:format>137 listova</dc:format>
  <dc:format>12683576 bytes</dc:format>
  <dc:language>srp</dc:language>
  <dc:date>2019</dc:date>
  <dc:contributor>Šmelcerović, Andrija 1973-</dc:contributor>
  <dc:contributor>Kocić, Gordana</dc:contributor>
  <dc:contributor>Agbaba, Danica</dc:contributor>
  <dc:contributor>Milić, Nataša</dc:contributor>
  <dc:contributor>Tasić-Kostov, Marija</dc:contributor>
</oai_dc:dc>
