Letters in Drug Design & Discovery - Volume 2, Issue 3, 2005

Inhibition of the blood fibrinolytic system (plasminogen/plasmin) occurs either at the level of plasminogen activators, regulated by specific plasminogen activator inhibitors (PAIs) or at the level of plasmin, mainly regulated by α2-antiplasmin (α2-AP). In this contribution, we focused on the roles of α2-AP in acute myocardial infarction and vascular remodeling associated with cardiovascular diseases. Our findings have identifi Read More

X-ray structure analysis of human factor VIIa/soluble tissue factor in complex with a peptide mimetic inhibitor reveals that Asp60, Tyr94, and Thr98 in the S2 site play an important role for the improvement of selectivity against thrombin.

Lectins are carbohydrate-binding proteins that can modulate cellular activity through cell membrane glycoproteins. A cell-based binding was set up to screen the lectin-like substances in natural products. Lectins, after binding to tumor cells, are detected with a biotinylated carbohydrate-polyacrylamide complex by ELISA. Sugar specificity can also be determined within the assay.

An expeditious four-step synthesis of the 1H-pyrrolo[2,3-f]quinoline-2-carboxamides (5a-h) is described. Readily available 6-quinolinecarboxaldehyde is converted to the parent acid (6) by nucleophilic attack of the azido-ester (9) and intramolecular cyclization of (10) followed by hydrolysis of the methyl ester (11). The cytotoxicity of the target molecules (5a-h) was evaluated in four tumour cell lines in Read More

Formulation ingredients may influence the pharmacokinetics of co-administered drugs. We investigated whether oral pre-dosing with the 'inactive' formulation ingredient Solutol affects the pharmacokinetic profile of intravenously administered colchicine in rats. Colchicine was administered intravenously to male Wistar rats as solution in isotonic sodium chloride (NaCl 0.9%, control group) at 1.5 mg/kg. A second group of rats Read More

Hyperthermia has been shown in many studies to be a strong sensitizer for cisplatin treatment and this sensitization may be in part due to the inhibition of DNA repair processes. We have set out to test this in cells with specific gene knockouts for known repair processes. The chicken DT40 cell system was used with a parental line (DT40) and knockouts of homologous recombination (HR) repair DT40Rad54, nonhomologous r Read More

A series of tartronic acid analogs of a non-peptide RGD mimetic were prepared and evaluated both for antagonism of the vitronectin receptor and for affinity to hydroxyapatite, the main inorganic component of bone matrix. The hydroxy bis acid unit was found to be optimal for both receptor binding and hydroxyapatite affinity, while the N-terminus affected only receptor binding affinity.

Estrone sulfatase (ES) is a membrane-bound enzyme that is responsible for maintaining high levels of estrogens in breast cancer cells. This may be due to the conversion of estrone-sulfate into estrone by estronesulfatase, which acts as a pool of potentially available estrogens. There is now abundant evidence that estrogens have a pivotal role in the growth and development of hormone-dependent breast cancer. Thus, inhibi Read More

We have identified a novel series of tricyclic pyrazinobenzodiazepines, represented by general structure 2, as potent vasopressin receptor antagonists. For example, 3 binds with high affinity to human V2 receptors and is very selective relative to V1a receptors. Compound (R)-(+)-3 exhibited pronounced aquaretic activity in rats and dogs on oral administration.

The synthesis and biological activities of a series of 2-amino-2-thioxoacetamide derivatives are described. These compounds have inhibitory effects against the protein tyrosine phosphatase activity of CD45. Compound 4i inhibited the PCA reaction in vivo.

Bullous pemphigoid and pemphigus vulgaris are blistering diseases. Our results show that expression of the integrins α6β4 α3β1is altered in both diseases: α6β4 to a greater extent in the former and α3β1 in the latter disease, respectively. Instead, the extracellular matrix examined resulted normally expressed.

The binding affinity (log nK) between human serum albumin and acidic drugs was quantitatively analyzed using a computational chemical method with several model phases. A flat guanidino-phase was the most efficient for calculating log nK values, and docking was easily performed. A flowerpot type model phase bonded a guanidino group at the center bottom demonstrating that ion-ion interaction was the main driving Read More

Oxidative stress is a major contributing factor to high mortality rates associated with several diseases such as sepsis. This condition can be controlled to a certain degree by antioxidants for instance ascorbic acid (vitamin C). This review focuses on the potential treatment of sepsis by ascorbic acid and its effects on the immune cell function.

Frontal dementia gives rise to characteristic behavioral changes, which include altered emotions, profound alterations in personality and social conduct, and behavioral alterations constitute core and supportive symptoms laid out in the diagnostic criteria. There are some behavioral symptoms which are considered specific for frontal dementia, being present in at least 50% of cases. These includes loss of basic emoti Read More

It has been suggested that resin wettability is advantageous for dietary phosphate binding in the gastrointestinal tract. To evaluate the effect of anion exchange resin wetting properties on in vivo phosphate binding ability, four types of ethylene glycol dimethacrylate cross-linking 4-vinylpyridinium anion exchange resins (EGDMA-4VP) were synthesized.