The effects of hydroxycoumarin derivatives on in vitro hemoglobin f induced

β-thalassemia and sickle cell anemia (SCD) are common hereditary blood diseases with current treatments having limitations as high cost and clinical complications. Since increased HbF in these patients reduces clinical severity, natural, or synthesized polyphenolic and antioxidant agents like resveratrol (that can reactivate HbF by inducing γ-globin gene expression) have lately become focus of research. The study aims to investigate the effects of dihydroxy-4-phenylcoumarin derivatives on fetal hemoglobin levels and γ-globin gene expression activation in K562 cell lines. Hydroxyurea being positive control, dihydroxy-4-phenylcoumarin derivatives K1, K2, K3 and K4 formed the study group. In the 4-phenyl ring of dihydroxy-4-phenylcoumarins, (K1, K2) and (K3, K4) are molecules containing hydroxy and methoxy substitution groups, respectively. Cell viability, total protein, total Hb, HbF and γ-globin gene expression analyzes were performed in K1, K2, K3, K4 and HU for HbF reactivation. 7,8-dihydroxy-4-phenylcoumarins showed more cytotoxic effects than 6,7-dihydroxy-4-phenylcoumarins. The highest HbF levels at 72 hours (compared with 50 μM HU concentration values) were K2>K3>K4≥K1>HU, and its γ-globin gene expression levels (compared with 200 μM HU concentration values) were K2>K3>K1>K4>HU. K2 0.8 μg/mL, which showed the highest HbF level, increased γ-globin gene expression levels 6.3 fold compared to HU 200 μM. Hydroxy substitutions at positions 7 and 8 for 4 phenylcoumarins were found to increase in γ-globin gene expression levels. It may be that the presence of methoxy substitutions result in a decrease in gene expression. Particularly, despite the cytotoxic effects of K2, it is considered that the significant increase in γ-globin gene expression levels may lead to HbF induction studies in different derivatives of 3- and 4-phenylcoumarins.