Thiourea derivatives induce fetal hemoglobin production in-vitro: A new class of potential therapeutic agents for β-thalassemia

Ali, Hamad; Iftikhar, Fizza; Shafi, Sarah; Siddiqui, Hamid Latif; Khan, Iltaf; Choudhary, Muhammad Iqbal; Musharraf, Syed Ghulam

doi:10.1016/j.ejphar.2019.05.027

Cited by 9 publications

(3 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Photophysical, electronic and magnetic properties of Schiff base metal complexes are deeply interested in a great number of researchers in material science 16–20 . Thiourea compounds are nitrogenous and sulfurous compounds 21 . They have diverse structures and applications.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, structural characterization and bioactivities of iron(III) and copper(II) complexes containing Schiff base thiourea ligands of 5‐(tert‐butyl)‐2‐hydroxybenzaldehyde

Trung,

Nam,

Van Tuyen

2024

Vietnam Journal of Chemistry

View full text Add to dashboard Cite

Azomethine and thiourea groups possess potential bioactive functions in pharmacological substances so organic ligands containing both imine and thiourea groups and their metal complexes will be expected to have remarkable bioactivities. In this study, some iron(III) and copper(II) complexes containing Schiff base thiourea ligands derived from 1‐(2‐aminoethyl)‐3‐phenylthiourea or 1‐(2‐aminophenyl)‐3‐phenylthiourea and 5‐(tert‐butyl)‐2‐hydroxybenzaldehyde were synthesized and characterized by modern physicochemical analysis approaches such as mass, infrared, UV–vis spectra and effective magnetic moments. The analytical data have supported for the structures of iron(III) complexes in the molecular ratio of 1:2 of iron(III) and the relative ligand while copper(II) complexes in the ratio of 1:1. The synthetic ligands coordinated with iron(III) as NO bidentate mode, however they chelated with copper(II) as NNOS tetradentate possibly. The obtained iron(III) complexes possess high‐spin octahedral geometry when copper(II) complexes perform distorted square planar. The obtained metal complexes were investigated in their thermal stability and chemical components by the thermogravimetric analysis. The synthetic Schiff base thiourea ligands were examined for their antimicrobial activity. Additionally, the synthesized complexes were estimated for their in vitro anticancer property against human cancer cell lines, hepatic cancer cells (HepG‐2), and lung adenocarcinoma cells (A549).

show abstract

Section: Introductionmentioning

confidence: 99%

“…[16][17][18][19][20] Thiourea compounds are nitrogenous and sulfurous compounds. 21 They have diverse structures and applications. Thioureas are usually used as intermediates in organic synthesis.…”

mentioning

confidence: 99%

Synthesis, structural characterization and bioactivities of iron(III) and copper(II) complexes containing Schiff base thiourea ligands of 5‐(tert‐butyl)‐2‐hydroxybenzaldehyde

Trung,

Nam,

Van Tuyen

2024

Vietnam Journal of Chemistry

View full text Add to dashboard Cite

show abstract

“…The hemoglobin containing cells were appeared as benzidine reactive cells (dark green) and non-erythroid cell as benzidineunreactive (color-less) as illustrated in Figure 2. We found that HU, a known HbF inducer as positive control showed maximal hemoglobin phenotype in K562 cells at 200 μM (EC50=54 μM), with significant increase in cellular size, when the cell proliferation was partly affected (Figure S1 and S2) (Ali et al, 2019). Initially, the dose dependent erythroid differentiating effect of the most effective compounds on K562 cells showed that, TDF at concentration of 12.5 μM induced erythroid differentiation with 45 ± 8.9 percent increase in benzidine positive cells.…”

Section: Tdf Induces K562 Erythroid Differentiationmentioning

confidence: 96%

Tenofovir disoproxil fumarate stimulates HbF production in K562 cells and β-YAC transgenic mice: A therapeutic approach for γ-globin induction

Khan¹,

Ali²,

Musharraf³

Authorea

Self Cite

View full text Add to dashboard Cite

Pharmacologic induction of fetal hemoglobin (HbF) is an effective strategy for treating β-hemoglobinopathies like β-thalassemia and sickle cell anemia by ameliorating disease severity. Hydroxyurea is the only FDA-approved agent that induces HbF, but significant non-responders and requirement for frequent monitoring of blood counts for drug toxicity limit clinical usefulness. Therefore, this study relates preclinical investigation of Tenofovir disoproxil fumarate (TDF) as a potential HbF inducing agent, using human erythroid cell line and a β-YAC mouse model. Erythroid induction of K562 cells was studied by the benzidine/H2O2 reaction, total hemoglobin production was estimated by plasma hemoglobin assay kit, and γ-globin gene expression by RT-qPCR, whereas, fetal hemoglobin production was estimated by flow cytometry and immunofluorescence microscopy. We observed significantly increased γ-globin gene transcription and HbF expression mediated by TDF in K562 cells. Subsequent treatment of β-YAC transgenic mice with TDF confirmed HbF induction in vivo through an increase in γ-globin gene expression and in the percentage of HbF positive red blood cells. Moreover, TDF showed no cytotoxic effect at HbF inducing concentrations. These data support the potential development of TDF for the treatment of hematological disorders, including β-thalassemia and sickle cell anemia.

show abstract

Acyclovir induces fetal hemoglobin via downregulation of γ-globin repressors, BCL11A and SOX6 trans-acting factors

Ali

Khan

Musharraf

2021

Biochemical Pharmacology

View full text Add to dashboard Cite

Thiourea derivatives induce fetal hemoglobin production in-vitro: A new class of potential therapeutic agents for β-thalassemia

Cited by 9 publications

References 57 publications

Synthesis, structural characterization and bioactivities of iron(III) and copper(II) complexes containing Schiff base thiourea ligands of 5‐(tert‐butyl)‐2‐hydroxybenzaldehyde

Synthesis, structural characterization and bioactivities of iron(III) and copper(II) complexes containing Schiff base thiourea ligands of 5‐(tert‐butyl)‐2‐hydroxybenzaldehyde

Tenofovir disoproxil fumarate stimulates HbF production in K562 cells and β-YAC transgenic mice: A therapeutic approach for γ-globin induction

Acyclovir induces fetal hemoglobin via downregulation of γ-globin repressors, BCL11A and SOX6 trans-acting factors

Contact Info

Product

Resources

About