Molecular Pharmacology, Vol 5, 455-462, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

Optical Studies of Drug-Protein Complexes

III. Interaction of Flufenamic Acid and Other N-Arylanthranilates with Serum Albumin

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland 20014

The extrinsic Cotton effects generated by the binding of flufenamic acid [N-(,,-trifluoro-m-tolyl)anthranilic acid], meclofenamic acid [N-(2,6-dichloro-m-tolyl)anthranilic acid], and mefenamic acid [N-(2,3-xylyl)anthranilic acid] to human serum albumin suggested that although these anti-inflammatory drugs are bound to the same binding site, each one takes up a unique spatial orientation to the protein. Extrinsic Cotton effects generated by the binding of flufenamic acid to different albumins indicated that time drug-binding sites on human, porcine, equine, and bovine serum albumins were similar, while those of canine, ovine, and rabbit serum albumins had somewhat different asymmetries. Spectral changes which accompanied the binding of flufenamic acid to human serum albumin strongly suggested that the aromatic portion of the drug was inserted into a hydrophobic crevice in the protein, while the carboxylate group of the drug interacted with a cationic site on the protein surface.

Note:
ACKNOWLEDGMENT It is a pleasure to acknowledge the skilled technical assistance of Mrs. D. K. Starkweather.