Binding of drugs to human serum albumin—I. circular dichroism studies on the binding of some analgesics, sedatives and antidepressive agents

Abstract

The possibility of using circular dichroism measurements as a method for studying drug-protein binding has been investigated with 52 analgesics, sedatives and antidepressive agents. The binding to human serum albumin (HSA) in 0·1 M KCl at pH 7.4 and 25–27° has been studied. New extrinsic Cotton effects have been obtained from HSA-complexes with 24 different drugs. Of the drugs known to form strong complexes with HSA, only p-acetanilides and acetylsalicylic acid failed to give extrinsic Cotton effects with HSA at the experimental conditions used. The structural requirement for binding of the drugs to HSA and the possibilities for studying the binding sites of HSA are discussed. In some cases (e.g. the benzdiazepine and dibenzazepine derivatives) a plane ring system with high electron density seems to be an essential factor for strong binding capacity.