Stereoselectivity and affinity in molecular pharmacology. III. Structural aspects in the mode of action of natural and synthetic auxins

Abstract

Analysis of available potency estimates for 35 pairs of enantiomeric arylcarboxylic acids with auxin activity (flax-root-growth inhibition test) revealed extensive correlations between the activity of the more potent and less potent isomers, as well as between the log of the ratio of potencies and the log potency of the more active isomer when structurally similar analogs are compared. 5 structural subgroups were discernible (n, eudismic-affinity quotient (EAQ), r2); (1) arylpropionic acids (6, -0.36, 0.66); (2) 2-naphthoxy-carboxylic acids (6, +1.07, 0.99); (3) 1-naphthoxycarboxylic acids (3, +1.56, 0.96); (4) ortho-substituted phenoxycarboxylic acids (10, +0.97, 0.96) and (5) ortho-unsubstituted phenoxycarboxylic acids (10, +0.56, 0.70). For achiral lower homologs such as auxin itself 3-indolyl-acetic acid (IAA), phenoxyacetic acid and 1-naphthoxyacetic acid, extrapolated potencies were found to agree well with experimental values. On the basis of these observations an auxin receptor is postulated and binding arrangements are described which explain most of the experimental data available. A 3-point attachment when allowed is the only binding mode compatible with the reported data.