title: Effect of anti-inflammatory thiosemicarbazone indoles on hyaluronidase, acid phosphatase and trypsin.
abstract: 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.
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000032:analysis*
chemical_list: D000893:Anti-Inflammatory Agents; D000135:Acid Phosphatase; D006821:Hyaluronoglucosaminidase; D014357:Trypsin