A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.

Original languageEnglish (US)
Pages (from-to)35-38
Number of pages4
JournalExperimental Hematology
Volume58
DOIs
StatePublished - Feb 1 2018

Fingerprint

Sickle Cell Anemia
Monocytes
Hydroxyurea
Cytokines
Thalidomide
Benzyl Compounds
Fetal Hemoglobin
Nitrates
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Morbidity
Mortality
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes. / Lanaro, Carolina; Franco-Penteado, Carla F.; Silva, Fabio H.; Fertrin, Kleber Y.; dos Santos, Jean Leandro; Wade, Marlene; Yerigenahally, Shobha; de Melo, Thais R.; Chin, Chung Man; Kutlar, Abdullah; Meiler, Steffen E; Costa, Fernando Ferreira.

In: Experimental Hematology, Vol. 58, 01.02.2018, p. 35-38.

Research output: Contribution to journalArticle

Lanaro, C, Franco-Penteado, CF, Silva, FH, Fertrin, KY, dos Santos, JL, Wade, M, Yerigenahally, S, de Melo, TR, Chin, CM, Kutlar, A, Meiler, SE & Costa, FF 2018, 'A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes', Experimental Hematology, vol. 58, pp. 35-38. https://doi.org/10.1016/j.exphem.2017.10.003
Lanaro, Carolina ; Franco-Penteado, Carla F. ; Silva, Fabio H. ; Fertrin, Kleber Y. ; dos Santos, Jean Leandro ; Wade, Marlene ; Yerigenahally, Shobha ; de Melo, Thais R. ; Chin, Chung Man ; Kutlar, Abdullah ; Meiler, Steffen E ; Costa, Fernando Ferreira. / A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes. In: Experimental Hematology. 2018 ; Vol. 58. pp. 35-38.
@article{87576979ad1e4b7a8cafbbe38fe28269,
title = "A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes",
abstract = "Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.",
author = "Carolina Lanaro and Franco-Penteado, {Carla F.} and Silva, {Fabio H.} and Fertrin, {Kleber Y.} and {dos Santos}, {Jean Leandro} and Marlene Wade and Shobha Yerigenahally and {de Melo}, {Thais R.} and Chin, {Chung Man} and Abdullah Kutlar and Meiler, {Steffen E} and Costa, {Fernando Ferreira}",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.exphem.2017.10.003",
language = "English (US)",
volume = "58",
pages = "35--38",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - A thalidomide–hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes

AU - Lanaro, Carolina

AU - Franco-Penteado, Carla F.

AU - Silva, Fabio H.

AU - Fertrin, Kleber Y.

AU - dos Santos, Jean Leandro

AU - Wade, Marlene

AU - Yerigenahally, Shobha

AU - de Melo, Thais R.

AU - Chin, Chung Man

AU - Kutlar, Abdullah

AU - Meiler, Steffen E

AU - Costa, Fernando Ferreira

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.

AB - Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.

UR - http://www.scopus.com/inward/record.url?scp=85036647241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036647241&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2017.10.003

DO - 10.1016/j.exphem.2017.10.003

M3 - Article

VL - 58

SP - 35

EP - 38

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

ER -