Biomaterial Database

Improving upon the in vitro biological activity of antithrombotic disulfides. 2004

Justin A MacDonald, and Maurice E Marchand, and Richard F Langler

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada. jmacdo@ucalgary.ca

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.

UI	MeSH Term	Description	Entries
D009574	Nitro Compounds	Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.	Nitrated Compounds
D010974	Platelet Aggregation	The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.	Aggregation, Platelet
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D004220	Disulfides	Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.	Disulfide
D005343	Fibrinolytic Agents	Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.	Antithrombic Drug,Antithrombotic Agent,Antithrombotic Agents,Fibrinolytic Agent,Fibrinolytic Drug,Thrombolytic Agent,Thrombolytic Agents,Thrombolytic Drug,Antithrombic Drugs,Fibrinolytic Drugs,Thrombolytic Drugs,Agent, Antithrombotic,Agent, Fibrinolytic,Agent, Thrombolytic,Agents, Antithrombotic,Drug, Antithrombic,Drug, Fibrinolytic,Drug, Thrombolytic,Drugs, Antithrombic
D005737	Garlic	A species of Allium used as a spice (SPICES) and traditional remedy. It contains alliin lyase and alliin, which is converted by alliin lyase to allicin, the pungent ingredient responsible for the aroma of fresh cut garlic.	Allium sativum
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular