Title:Synthesis and Erythroid Induction Activity of New Thiourea Derivatives
Volume: 17
Issue: 2
Author(s): Hina Siddiqui*, Sarah Shafi, Hamad Ali and Syed Ghulam Musharraf
Affiliation:
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270,Pakistan
Keywords:
Thiourea derivatives, erythroid induction activity, cytotoxicity, β-thalassemia, HbF induction effect, sickle-cell
anemia and β-thalassemia.
Abstract: Background: The use of medicinal agents to augment the fetal hemoglobin (HbF) accretion is
an important approach for the treatment of sickle-cell anemia and β-thalassemia. HbF inducers have the
potential to reduce the clinical symptoms and blood transfusion dependence in the patients of β-
hemoglobinopathies.
Objective: The current study was aimed to examine the erythroid induction potential of newly synthesized
thiourea derivatives.
Methods: Thiourea derivatives 1-27 were synthesized by using environmentally friendly methods.
Compounds 3, 10 and 22 were found to be new. The structures of synthesized derivatives were deduced
by using various spectroscopic techniques. These derivatives were then evaluated for their
erythroid induction using the human erythroleukemic K562 cell line, as a model. The benzidine-H2O2
assay was used to evaluate erythroid induction, while HbF expression was studied through immunocytochemistry
using the Anti-HbF antibody. Cytotoxicity of compounds 1-27 was also evaluated on mouse
fibroblast 3T3 cell line and cancer Hela cell line using MTT assay.
Result: All the compounds (1-27) have not been reported for their erythroid induction activity previously.
Compounds 1, 2, and 3 were found to be the potent erythroid inducing agents with % induction of
45± 6.9, 44± 5.9, and 41± 6.1, at 1.56, 0.78, and 0.78 μM concentrations, respectively, as compared to
untreated control (12 ± 1 % induction). Furthermore, compound 1, 2, and 3 significantly induced fetal
hemoglobin the expression up to 4.2-fold, 4.06-fold, and 3.52-fold, respectively, as compared to untreated
control. Moreover, the compounds 1-4, 6-9, 11, 12, 15, 17, 19, 22, 23, and 25 were found to be
non-cytotoxic against the 3T3 cell line.
Conclusion: This study signifies that the compounds reported here may serve as the starting point for
the designing and development of new fetal hemoglobin inducers for the treatment of β-
hemoglobinopathies.
