Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds
| Autor: | Gulsah Bayraktar, Ali Ahmet Kilimcioğlu, Hasan Akbaba, Huseyin Istanbullu, Bilge Debeleç Bütüner, İbrahim Çavuş, Ercin Erciyas, Gunes Coban, Ahmet Özbilgin, Vildan Alptüzün |
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| Přispěvatelé: | Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Izmir Katip Celebi University, Cigli, Izmir, Turkey, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey, Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey, Department of Parasitology, Manisa Celal Bayar University, Manisa, Turkey, Ege Üniversitesi |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Leishmania tropica Antiprotozoal Agents Pharmaceutical Science antileishmanial Mice Structure-Activity Relationship Parasitic Sensitivity Tests Drug Discovery 4-d]pyrimidine Animals Leishmania major Enzyme Inhibitors PTR1 enzyme inhibition Amastigote Cytotoxicity neglected disease chemistry.chemical_classification thiazolo[5 biology Dose-Response Relationship Drug Molecular Structure Chemistry Drug discovery Macrophages biology.organism_classification In vitro Thiazoles Enzyme Pyrimidines RAW 264.7 Cells Biochemistry Enzyme inhibitor Drug Design biology.protein Oxidoreductases |
| Popis: | A series of thiazolopyrimidine derivatives was designed and synthesized as aLeishmania majorpteridine reductase 1 (LmPTR1) enzyme inhibitor. TheirLmPTR1 inhibitor activities were evaluated using the enzyme produced byEscherichia coliin a recombinant way. the antileishmanial activity of the selected compounds was tested in vitro againstLeishmaniasp. 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, compoundL16exhibited an antileishmanial activity for both the promastigote and amastigote forms ofL. tropica, with IC(50)values of 7.5 and 2.69 mu M, 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. Turkiye Bilimsel ve Teknolojik Arastirma KurumuTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG-213-S026]; Ege Universitesi [2014BIL003] Turkiye Bilimsel ve Teknolojik Arastirma Kurumu, Grant/Award Number: SBAG-213-S026; Ege Universitesi, Grant/Award Number: 2014BIL003 |
| Databáze: | OpenAIRE |
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