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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Discovery of phenylsulfonylfuroxan derivatives as gamma globin inducers by histone acetylation

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Ferreira de Melo, Thais Regina [1] ; Kumkhaek, Chutima [2] ; dos Santos Fernandes, Guilherme Felipe [1] ; Lopes Pires, Maria Elisa [3] ; Chelucci, Rafael Consolin [1] ; Barbieri, Karina Pereira [1] ; Coelho, Fernanda [4] ; de Oliveira Capote, Ticiana Sidorenko [4] ; Lanaro, Carolina [3] ; Carlos, Iracilda Zeppone [1] ; Marcondes, Sisi [3] ; Chegaev, Konstantin [5] ; Guglielmo, Stefano [5] ; Fruttero, Roberta [5] ; Chung, Man Chin [1] ; Costa, Fernando Ferreira [3] ; Rodgers, Griffin P. [2] ; dos Santos, Jean Leandro [1]
Total Authors: 18
[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Araraquara - Brazil
[2] NHLBI, Mol & Clin Hematol Branch, Bldg 10, Bethesda, MD 20892 - USA
[3] State Univ Campinas UNICAMP, Fac Med Sci, BR-13083970 Campinas, SP - Brazil
[4] Sao Paulo State Univ UNESP, Sch Dent, BR-14801903 Araraquara - Brazil
[5] Univ Torino, Dipartimento Sci & Tecnol Farmaco, I-10124 Turin - Italy
Total Affiliations: 5
Document type: Journal article
Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 154, p. 341-353, JUN 25 2018.
Web of Science Citations: 1

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-alpha, 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 gamma-globin in K562 cells at 100 mu M. The mechanisms involved in the gamma-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. (C) 2018 Elsevier Masson SAS. All rights reserved. (AU)

FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
Grantee:Fernando Ferreira Costa
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/12495-6 - Optimization, synthesis and pharmacological evaluation of new drug candidates to treat the symptoms of sickle cell disease
Grantee:Jean Leandro dos Santos
Support type: Regular Research Grants
FAPESP's process: 14/06755-6 - Synthesis and pharmacological evaluation of new pomalidomide derivatives to treat sickle cell disease symptoms
Grantee:Thaís Regina Ferreira de Melo
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/09502-7 - Design, synthesis and antitubercular activity of new oxazolidinones useful for the treatment of multidrug-resistant tuberculosis
Grantee:Guilherme Felipe dos Santos Fernandes
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/04244-1 - Synthesis, structural characterization and NO-donor evaluation of hybrid compounds useful to treat sickle cell disease symptoms
Grantee:Thaís Regina Ferreira de Melo
Support type: Scholarships abroad - Research Internship - Master's degree