Inhibitors of Yellow Fever Virus replication based on 1,3,5-triphenyl-4,5-dihydropyrazole scaffold: Design, synthesis and antiviral evaluation
| العنوان: | Inhibitors of Yellow Fever Virus replication based on 1,3,5-triphenyl-4,5-dihydropyrazole scaffold: Design, synthesis and antiviral evaluation |
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| المؤلفون: | Rossella Fioravanti, Nicoletta Desideri, Roberta Loddo, Antonio Carta, Gabriella Collu, Ilenia Delogu, Elena Maria Atzori |
| المصدر: | European Journal of Medicinal Chemistry. 141:15-25 |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell Survival, Stereochemistry, Pyrazoline, Microbial Sensitivity Tests, Virus Replication, Antiviral Agents, 01 natural sciences, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Flaviviridae, chemistry.chemical_compound, Cricetinae, Drug Discovery, Animals, Structure–activity relationship, Potency, Cytotoxicity, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Pestivirus, Haplorhini, General Medicine, biology.organism_classification, Virology, 0104 chemical sciences, Flavivirus, 4,5-dihydropyrazole derivatives, antiviral activity, BVDV, RNA and DNA viruses, 030104 developmental biology, Viral replication, Drug Design, Pyrazoles, Cattle, Yellow fever virus |
| الوصف: | By the antiviral screening of an in house library of pyrazoline compounds, 4-(3-(4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide (5a) was identified as a promising hit compound for the development of anti- Yellow Fever Virus (YFV) agents. Structural optimization studies were focused on the development of 5a analogues which retain the potency as YFV inhibitors and show a reduced cytotoxicity. The synthesized 1-3,5-triphenyl-pyrazolines (4a-j, 5a-j, 6a-j) were evaluated in cell based assays for cytotoxicity and antiviral activity against representative viruses of two of the three genera of the Flaviviridae family, i.e.: Pestivirus (BVDV) and Flavivirus (YFV). These compounds were also tested against a large panel of different pathogenic RNA and DNA viruses. Most of the new 1-3,5-triphenyl-pyrazolines (4a-j, 5a-j, 6a-j) exhibited a specific activity against YFV, showing EC50 values in the low micromolar range with almost a 10-fold improvement in potency compared to the reference inhibitor 6-azauridine. However, the selectivity indexes of the unsubstituted (4a-j) and the phenoxy (5a-j) analogues were generally modest due to the pronounced cytotoxicity against BHK-21 cells. Otherwise, the benzyloxy derivatives (6a-j) generally coupled high potency and selectivity. On the basis of both anti-YFV activity and selectivity index, pyrazolines 6a and 6b were chosen for time of addition experiments. The selected pyrazolines and the reference inhibitor 6-azauridine displayed maximal inhibition when added in the pretreatment or during the infection. |
| تدمد: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2017.09.060 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc11d8c2565c841ed2909ca13ea970c9 https://doi.org/10.1016/j.ejmech.2017.09.060 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....dc11d8c2565c841ed2909ca13ea970c9 |
| قاعدة البيانات: | OpenAIRE |
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