Resveratrol (RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1-64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + γA), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.
class="Chemical">Resveratrol (n class="Chemical">RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1-64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + γA), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.
Authors: Sophie Lanzkron; C Patrick Carroll; Peter Hill; Mandy David; Nicklaine Paul; Carlton Haywood Journal: Am J Hematol Date: 2015-02-25 Impact factor: 10.047
Authors: Carolina Lanaro; Carla F Franco-Penteado; Fabio H Silva; Kleber Y Fertrin; Jean Leandro Dos Santos; Marlene Wade; Shobha Yerigenahally; Thais R de Melo; Chung Man Chin; Abdullah Kutlar; Steffen E Meiler; Fernando Ferreira Costa Journal: Exp Hematol Date: 2017-11-03 Impact factor: 3.084
Authors: Thassila N Pitanga; Ricardo R Oliveira; Dalila L Zanette; Caroline C Guarda; Rayra P Santiago; Sanzio S Santana; Valma M L Nascimento; Jonilson B Lima; Graziele Q Carvalho; Vitor V Maffili; Magda O S Carvalho; Luiz C J Alcântara; Valéria M Borges; Marilda S Goncalves Journal: Cytokine Date: 2016-04-02 Impact factor: 3.861
Authors: Thais Regina Ferreira de Melo; Brian M Dulmovits; Guilherme Felipe Dos Santos Fernandes; Cristiane M de Souza; Carolina Lanaro; Minghzu He; Yousef Al Abed; Man Chin Chung; Lionel Blanc; Fernando Ferreira Costa; Jean Leandro Dos Santos Journal: Bioorg Chem Date: 2021-06-10 Impact factor: 5.307
Authors: Aline Renata Pavan; Juliana Romano Lopes; Carlos Henrique Lima Imperador; Chung Man Chin; Jean Leandro Dos Santos Journal: Front Med (Lausanne) Date: 2022-09-08
Authors: Leandro da Costa Clementino; Guilherme Felipe Santos Fernandes; Igor Muccilo Prokopczyk; Wilquer Castro Laurindo; Danyelle Toyama; Bruno Pereira Motta; Amanda Martins Baviera; Flávio Henrique-Silva; Jean Leandro Dos Santos; Marcia A S Graminha Journal: PLoS One Date: 2021-11-01 Impact factor: 3.240