Improving upon the in vitro biological activity of antithrombotic disulfides.
Several sulfur-containing compounds, isolated from garlic, have been implicated as highly active antithrombotic agents. We have prepared 10 new aromatic disulfides and an aromatic thiosulfonate in order to determine the in vitro response of human platelets to dosages of these compounds. The poor biological activity of PhSSCH3 was enhanced by the introduction of, inter alia, a nitro group onto the aromatic ring. The nitro group increased potency by activating the disulfide linkage. Anti-platelet aggregation activity was also enhanced by increasing the lipophilicity of one test compound. The ability of an aromatic disulfide to inhibit platelet aggregation can be enhanced by appending an electron-withdrawing group to the aromatic ring. The results presented establish that the aromatic thiosulfonate is a very effective inhibitor of platelet aggregation.
MacDonald
Justin A
JA
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada. jmacdo@ucalgary.ca
Marchand
Maurice E
ME
Langler
Richard F
RF
D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005737:Garlic / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004220:Disulfides; D005343:Fibrinolytic Agents; D009574:Nitro Compounds; D010975:Platelet Aggregation Inhibitors