Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases.
Lipoxygenases (LO) have been implicated in asthma, immune disorders, and various cancers and as a consequence, there is great interest in isolating selective LO isozyme inhibitors. Currently, there is much use of baicalein as a selective human platelet 12-LO (12-hLO) inhibitor, however, our current steady-state inhibition data indicate that baicalein is not selective against 12-hLO versus human reticulocyte 15-LO-1 (15-hLO-1) (15/12=1.3), in vitro. However, in the presence of detergents baicalein is slightly more selective (15/12=7) as seen by the steady-state inhibition kinetics, which may imply greater selectivity in a cell-based assay but has yet to be proven. The mechanism of baicalein inhibition of 15-hLO-1 is reductive, which molecular modeling suggests is through direct binding of the catecholic moiety of baicalein to the iron. A structurally related flavonoid, apigenin, is not reductive, however, molecular modeling suggests a hydrogen bond with Thr591 may account for its inhibitor potency.
Deschamps
Joshua D
JD
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Kenyon
Victor A
VA
Holman
Theodore R
TR
D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D001092:Arachidonate 12-Lipoxygenase / Q000302:isolation & purification; D001093:Arachidonate 15-Lipoxygenase / Q000302:isolation & purification; D001665:Binding Sites; D001792:Blood Platelets / Q000201:enzymology*; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D016859:Lipoxygenase Inhibitors; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D012156:Reticulocytes / Q000201:enzymology*; D013329:Structure-Activity Relationship
D044950:Flavanones; D008024:Ligands; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D047310:Apigenin; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase