Effect of anti-inflammatory thiosemicarbazone indoles on hyaluronidase, acid phosphatase and trypsin.

The present study was designed to evaluate the molecular basis of anti-inflammatory effects of nine 2-aryl-3-[4-(substituted phenyl)-3-thiosemicarbazone] indoles and their interaction with lysosomal and proteolytic enzymes. All compounds exhibited anti-inflammatory activity, which was reflected by 5-67% reduction in carrageenin-induced oedema in rat. Substituted thiosemicarbazone indoles caused concentration-dependent inhibition of hyaluronidase activity in vitro while the activities of acid phosphatase and trypsin were unaltered. Substitution of the aryl group attached to indole moiety resulted in a 2- to 3-fold increase in hyaluronidase inhibition by these compounds. Preincubation of the compounds with hyaluronidase produced time-dependent inactivation of the enzyme. Determination of enzyme inhibition kinetics with 2-aryl-3-[4-(2-methylphenyl)-3-thiosemicarbazone] indole by Lineweaver-Burk and Dixon plots indicated competitive nature of hyaluronidase-compound interaction. These studies failed to demonstrate any definite relationship between anti-inflammatory activity and hyaluronidase inhibition.