Discovery of phenylsulfonylfuroxan derivatives as gamma globin inducers by histone acetylation
| Autor: | Konstantin Chegaev, Fernando Ferreira Costa, Chutima Kumkhaek, Ticiana Sidorenko de Oliveira Capote, Jean Leandro dos Santos, Roberta Fruttero, Thais Regina Ferreira de Melo, Man Chin Chung, Rafael Consolin Chelucci, Carolina Lanaro, Karina Pereira Barbieri, Iracilda Zeppone Carlos, Griffin P. Rodgers, Guilherme Felipe dos Santos Fernandes, Fernanda Coelho, Sisi Marcondes, Maria Elisa Lopes Pires, Stefano Guglielmo |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade Estadual de Campinas (UNICAMP), Università degli Studi di Torino |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Analgesic activity Cell Anemia Sickle Cell Pharmacology Antiplatelet activity Epigenetic Fetal hemoglobin Furoxan Sickle cell disease Acetic Acid Acetylation Dose-Response Relationship Drug Histones Humans K562 Cells Molecular Structure Nitric Oxide Oxadiazoles Structure-Activity Relationship gamma-Globins Drug Discovery Drug Discovery3003 Pharmaceutical Science Organic Chemistry Nitric oxide Dose-Response Relationship 03 medical and health sciences chemistry.chemical_compound medicine Structure–activity relationship biology Monocyte Anemia General Medicine Sickle Cell 030104 developmental biology medicine.anatomical_structure Histone chemistry biology.protein Tumor necrosis factor alpha Drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| Popis: | Made available in DSpace on 2018-12-11T17:37:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-25 N-oxide derivatives 5(a-b), 8(a-b), and 11(a-c) were designed, synthesized and evaluated in vitro and in vivo as potential drugs that are able to ameliorate sickle cell disease (SCD) symptoms. All of the compounds demonstrated the capacity to releasing nitric oxide at different levels ranging from 0.8 to 30.1%, in vivo analgesic activity and ability to reduce TNF-α levels in the supernatants of monocyte cultures. The most active compound (8b) protected 50.1% against acetic acid-induced abdominal constrictions, while dipyrone, which was used as a control only protected 35%. Compounds 8a and 8b inhibited ADP-induced platelet aggregation by 84% and 76.1%, respectively. Both compounds increased γ-globin in K562 cells at 100 μM. The mechanisms involved in the γ-globin increase are related to the acetylation of histones H3 and H4 that is induced by these compounds. In vitro, the most promising compound (8b) was not cytotoxic, mutagenic and genotoxic. São Paulo State University (UNESP) School of Pharmaceutical Sciences Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, United States Faculty of Medical Sciences State University of Campinas - UNICAMP São Paulo State University (UNESP) School of Dentistry Dipartimento di Scienza e Tecnologia del Farmaco Università degli Studi di Torino São Paulo State University (UNESP) School of Pharmaceutical Sciences São Paulo State University (UNESP) School of Dentistry |
| Databáze: | OpenAIRE |
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