Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds

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dc.contributor.authorIstanbullu H.
dc.contributor.authorBayraktar G.
dc.contributor.authorAkbaba H.
dc.contributor.authorCavus I.
dc.contributor.authorCoban G.
dc.contributor.authorDebelec Butuner B.
dc.contributor.authorKilimcioglu A.A.
dc.contributor.authorOzbilgin A.
dc.contributor.authorAlptuzun V.
dc.contributor.authorErciyas E.
dc.date.accessioned2024-07-22T08:07:19Z
dc.date.available2024-07-22T08:07:19Z
dc.date.issued2020
dc.description.abstractA series of thiazolopyrimidine derivatives was designed and synthesized as a Leishmania major pteridine reductase 1 (LmPTR1) enzyme inhibitor. Their LmPTR1 inhibitor activities were evaluated using the enzyme produced by Escherichia coli in a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro against Leishmania sp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compound L16 exhibited an antileishmanial activity for both the promastigote and amastigote forms of L. tropica, with IC50 values of 7.5 and 2.69 µM, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery. © 2020 Deutsche Pharmazeutische Gesellschaft
dc.identifier.DOI-ID10.1002/ardp.201900325
dc.identifier.issn03656233
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13922
dc.language.isoEnglish
dc.publisherWiley-VCH Verlag
dc.subjectAnimals
dc.subjectAntiprotozoal Agents
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug Design
dc.subjectEnzyme Inhibitors
dc.subjectLeishmania major
dc.subjectMacrophages
dc.subjectMice
dc.subjectModels, Molecular
dc.subjectMolecular Structure
dc.subjectOxidoreductases
dc.subjectParasitic Sensitivity Tests
dc.subjectPyrimidines
dc.subjectRAW 264.7 Cells
dc.subjectStructure-Activity Relationship
dc.subjectThiazoles
dc.subject2 bromo n (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)benzamide
dc.subject2 chloro n (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)benzamide
dc.subject2,4 dichloro n (5 chlorothiazolo[5 4 d]pyrimidin 2 yl)benzamide
dc.subject4 chloro n (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)benzamide
dc.subjectamphotericin B
dc.subjectantileishmanial agent
dc.subjectenzyme inhibitor
dc.subjectmeglumine antimonate
dc.subjectmethotrexate
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 2 trifluoromethylbenzamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 3 phenylpropionamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 4 fluorobenzamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 4 methoxybenzamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 4 methylbenzamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl) 4 nitrobenzamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl)cinnamamide
dc.subjectn (5 chlorothiazolo[5 4 d]pyrimidin 2 yl)furan 2 carboxamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl) 2 iodobenzamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)2 fluorobenzamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)2 methoxybenzamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)2 methylbenzamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)acetamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)benzamide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)butyramide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)isobutyramide
dc.subjectn (5 chlorothiazolo[5,4 d]pyrimidin 2 yl)propionamide
dc.subjectn (5 chlorothiazolo[5,4 d]]pyrimidin 2 yl)cyclohexane carboxamide
dc.subjectoxidoreductase
dc.subjectpteridine reductase 1
dc.subjectpyrimidine derivative
dc.subjectunclassified drug
dc.subjectantiprotozoal agent
dc.subjectenzyme inhibitor
dc.subjectoxidoreductase
dc.subjectpteridine reductase
dc.subjectpyrimidine derivative
dc.subjectthiazole derivative
dc.subjectamastigote
dc.subjectanimal cell
dc.subjectantileishmanial activity
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectdrug cytotoxicity
dc.subjectdrug design
dc.subjectdrug synthesis
dc.subjectenzyme inhibition
dc.subjectIC50
dc.subjectin vitro study
dc.subjectLeishmania major
dc.subjectLeishmania tropica
dc.subjectmolecular docking
dc.subjectmolecular dynamics
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectpromastigote
dc.subjectprotein expression
dc.subjectRAW 264.7 cell line
dc.subjectanimal
dc.subjectchemical structure
dc.subjectchemistry
dc.subjectdose response
dc.subjectdrug effect
dc.subjectdrug sensitivity
dc.subjectenzymology
dc.subjectmacrophage
dc.subjectmetabolism
dc.subjectmolecular model
dc.subjectmouse
dc.subjectstructure activity relation
dc.subjectsynthesis
dc.titleDesign, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds
dc.typeArticle

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