Analysis of Structural Requirements for Ah Receptor Antagonist Activity: Ellipticines, Flavones, and Related Compounds

摘要: A number of studies have examined the structure-activity relationships for agonist activity Ah receptor (AhR) ligands. Fewer considered structural basis potential antagonist properties. Certain ellipticine derivatives been reported to bind AhR and inhibit ability 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transform a form that recognizes dioxin-responsive enhancer element (DRE) upstream cytochrome P4501A1 gene. In present study, over 30 structurally related compounds were their AhR, activate it DRE-binding form, induce luciferase gene under control DRE-containing enhancer, block activation by TCDD. The several TCDD-elicited DRE binding TCDD-induced was inversely alone stimulate these responses. most potent good characteristics in terms conforming previously predicted 14 x 12 5 van der Waals dimensions presence an electron-rich ring nitrogen at or near relatively unsubstituted X-axis terminal position. Based on data, flavone synthesized tested relative agonist/antagonist activity. These additional data consistent with hypothesis center along lateral position cavity is characteristic enhances