27-Nor-Δ4-dafachronic acid is a synthetic ligand of Caenorhabditis elegans DAF-12 receptor. . 2013 Mar 28. doi:pii: S0960-894X(13)00399-5. 10.1016/

SAMAJA GA; CASTRO O; ALVAREZ LD; DANSEY MV; ESCUDERO DS; VELEIRO AS; A. PECCI; BURTON G.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2013 p. 399 - 410

0960-894X

27-Nor-Δ4-dafachronic acid was prepared in nine steps and 14% overall yield by two sequential 2-carbon homologations from 20β-carboxyaldehyde-4-pregnen-3-one. Its activity was evaluated in vivo, where it rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants and restored their normal resistance to oxidative stress. 27-Nor-Δ4-dafachronic acid was also able to directly bind and activate DAF-12 in a transactivation cell-based luciferase reporter assay, although it was less active than the corresponding 25R-and 25S dafachronic acids. The binding mode of the 27-Nor steroid was studied by molecular dynamics using a homology model of the CeDAF-12 receptor.