Aslam M A Mazari1, Usama M Hegazy2, Bengt Mannervik3. 1. Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden. 2. Molecular Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, 12311 Cairo, Egypt. 3. Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: Bengt.Mannervik@neurochem.su.se.
Abstract
OBJECTIVE: Hematopoietic prostaglandin D2 synthase (HPGDS) is a member of the Sigma class glutathione transferases (GSTs) catalyzing the isomerization of prostaglandin H2 to prostaglandin D2, a mediator of allergy and inflammation responses. Selective inhibitors of human HPGDS are expected to be of therapeutic importance in relieving symptoms related to allergy and asthma. Hence, a collection of diverse FDA-approved compounds was screened for potential novel applications as inhibitors of HPGDS. METHODS: The catalytic activity of purified HPGDS was used for inhibition studies in vitro. RESULTS: Our inhibition studies revealed 23 compounds as effective inhibitors of HPGDS with IC50 values in the low micromolar range. Erythrosine sodium, suramin, tannic acid and sanguinarine sulfate were characterized with IC50 values of 0.2, 0.3, 0.4, and 0.6 μM, respectively. Kinetic inhibition analysis showed that erythrosine sodium is a nonlinear competitive inhibitor of HPGDS, while suramin, tannic acid and sanguinarine sulfate are linear competitive inhibitors. CONCLUSION: The results show that certain FDA-approved compounds may have pharmacological effects not previously realized that warrant further consideration in their clinical use.
OBJECTIVE:Hematopoietic prostaglandin D2 synthase (HPGDS) is a member of the Sigma class glutathione transferases (GSTs) catalyzing the isomerization of prostaglandin H2 to prostaglandin D2, a mediator of allergy and inflammation responses. Selective inhibitors of humanHPGDS are expected to be of therapeutic importance in relieving symptoms related to allergy and asthma. Hence, a collection of diverse FDA-approved compounds was screened for potential novel applications as inhibitors of HPGDS. METHODS: The catalytic activity of purified HPGDS was used for inhibition studies in vitro. RESULTS: Our inhibition studies revealed 23 compounds as effective inhibitors of HPGDS with IC50 values in the low micromolar range. Erythrosine sodium, suramin, tannic acid and sanguinarine sulfate were characterized with IC50 values of 0.2, 0.3, 0.4, and 0.6 μM, respectively. Kinetic inhibition analysis showed that erythrosine sodium is a nonlinear competitive inhibitor of HPGDS, while suramin, tannic acid and sanguinarine sulfate are linear competitive inhibitors. CONCLUSION: The results show that certain FDA-approved compounds may have pharmacological effects not previously realized that warrant further consideration in their clinical use.
Authors: A Hernandez-Carretero; N Weber; M R La Frano; W Ying; J Lantero Rodriguez; D D Sears; V Wallenius; E Börgeson; J W Newman; O Osborn Journal: Int J Obes (Lond) Date: 2017-11-01 Impact factor: 5.095