Positional preferences in flavonoids for inhibition of ribonuclease A: Where “OH” where?

Abstract

Flavonoids are a class of polyphenols that possess diverse properties. The structure‐activity relationship of certain flavonoids and resveratrol with ribonuclease A (RNase A) has been investigated. The selected flavonoids have a similar skeleton and the positional preferences of the phenolic moieties toward inhibition of the catalytic activity of RNase A have been studied. The results obtained for RNase A inhibition by flavonoids suggest that the planarity of the molecules is necessary for effective inhibitory potency. Agarose gel electrophoresis and precipitation assay experiments along with kinetic studies reveal Ki values for the various flavonoids in the micromolar range. Minor secondary structural changes of RNase A were observed after interaction with the flavonoids. An insight into the specific amino acid involvement in the binding of the substrate using docking studies is also presented. The dipole moment of the flavonoids that depends on the orientation of the hydroxyl groups in the molecule bears direct correlation with the inhibitory potency against RNase A. The direct association of this molecular property with enzyme inhibition can be exploited for the design and development of inhibitors of proteins.

Targeting the aryl hydrocarbon receptor by gut phenolic metabolites: A strategy towards gut inflammation

“…Thus, the planar conformation, and also hydroxyl groups present in the B and C rings of flavonoids ( Fig. 4 ) could be related to these compounds being AHR ligands [ 264 ]. Nevertheless, other structurally different molecules as potential AHR modulators should not be disregarded and be evaluated and studied in detail in the future.…”