Screening for selective thrombin inhibitors in mushrooms

Thrombin is the key serine proteinase of the coagulation cascade and theref ore a suitable target for inhibition of blood coagulation. A number of phar macologically active secondary metabolites from mushrooms have already been isolated, thus providing the rationale for screening for new thrombin inhi bitors in mushrooms. In this study, inhibitory activities of mushroom extra cts on thrombin and trypsin were measured using the chromogenic substrates H-D-phenylalanine-L-pipecolyl-L-arginine-paranitroaniline dihydrochloride ( S-2238) for thrombin and N-benzoyl-D,L-Arg-p-nitroanilide (BAPNA) for tryps in. The inhibitory activities of extracts from 95 Basidiomycete species hav e been determined. The majority of samples inhibited trypsin and thrombin w ith various potencies; however, some extracts showed no activity against on e or both of the enzymes. An aqueous extract of Gleophyllum odoratum exhibi ted high inhibitory activity on both thrombin and trypsin (72 and 60%, resp ectively), while extracts of Clitocybe gibba, Amanita virosa, Cantharellus lutescens, Suillus tridentinus, Hypoloma fasciculare and Lactarius badiosan guineus considerably inhibited thrombin (49, 48, 36, 34, 32 and 31%, respec tively) and showed no inhibitory activity on trypsin. The results at this p oint are promising for further research with the objective of finding an ef fective and safe thrombin inhibitor. (C) 2001 Lippincott Williams & Wilkins .