Gerd Dannhardt

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Prostaglandins are formed from arachidonic acid by the action of cyclooxygenase and subsequent downstream synthetases. Two closely related forms of the cyclooxygenase have been identified which are now known as COX-1 and COX-2. Both isoenzymes transform arachidonic acid to prostaglandins, but differ in their distribution and their physiological roles.(More)
Vanillin, a food flavoring agent, has been shown to suppress cancer cell migration and metastasis in a mouse model, but its mechanism of action is unknown. In this report, we have examined the antimetastatic potential of vanillin and its structurally related compounds, vanillic acid, vanillyl alcohol, and apocynin on hepatocyte growth factor (HGF)-induced(More)
A novel class of nonantioxidant dual inhibitors of both CO and 5-LO is described. The balance between the activity against CO and 5-LO can be shifted by modifying the substitution pattern of the phenyl moiety at the 6-position of the pyrrolizine ring. Structure-activity relationships are discussed. Compound 3e with a 4-Cl substituent (IC50 = 0.21 microM(More)
2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl, 2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid (ML 3000) is a dual inhibitor of the enzymes cyclo-oxygenase and 5-lipoxygenase in bovine and human thrombocytes and granulocytes. In animal experiments the compound has antiphlogistic, analgesic, antipyretic, antiasthmatic and antiaggregative activity at a dosage that(More)
The identification and characterisation of the isoenzyme cyclooxygenase 2 (COX-2) stimulated investigations to develop efficient non-steroidal anti-inflammatory drugs with reduced side effects compared to standard NSAIDs. This review will focus on the structural features needed to achieve COX-2 selectivity. Five structural classes can be identified together(More)
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds(More)
An automated method for simultaneous routine quantification of the antipsychotic drugs clozapine, olanzapine and their demethylated metabolites is described. The method included adsorption on a cyanopropyl (CPS) coated clean-up column (10 microm; 10 x 2.0 mm I.D.), washing off interfering serum constituents to waste, and separation on C18 ODS Hypersil(More)
Drugs used to treat various disorders target GABA A receptors. To develop alpha subunit selective compounds, we synthesized 5-(4-piperidyl)-3-isoxazolol (4-PIOL) derivatives. The 3-isoxazolol moiety was substituted by 1,3,5-oxadiazol-2-one, 1,3,5-oxadiazol-2-thione, and substituted 1,2,4-triazol-3-ol heterocycles with modifications to the basic piperidine(More)
The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into(More)
A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and(More)