Hina Siddiqui*, Sarah Shafi, Hamad Ali and Syed Ghulam Musharraf Pages 1 - 13 ( 13 )
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 potential to reduce the clinical symptoms and blood transfusion dependence in the patients of β-hemoglobinopathies.
Objectives: Current study was aimed to examine the erythroid induction potential of newly synthesized thiourea derivatives.
Methods: Thiourea derivatives 1-27 were synthesized by using environmental 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 human erythroleukemic K562 cell line, as a model. Benzidine-H2O2 assay was used to evaluate erythroid induction, while HbF expression was studied through immunocytochemistry using 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 compare 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 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.
Thiourea derivatives, erythroid induction activity, cytotoxicity, β-thalassemia, HbF induction effect
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,University of Karachi, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,University of Karachi, Dr. Panjwani Center for Molecular Medicine and Drug Research; International Center for Chemical and Biological Sciences, University of Karachi, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,University of Karachi