Letters in Drug Design & Discovery - Volume 1, Issue 4, 2004

Both enveloped and non-enveloped viruses from different families may use heparan sulfates (HS) to bind to and / or enter into their host cells. The interactions between viruses and HS can be inhibited by a novel class of antiviral compounds, the N,N'-bisheteryl derivatives of 3,12-diaza-6,9-diazoniadispiro(5,2,5,2) hexadecane which bind to specific structural moieties of HS. By this way these compounds block adsorption of vi Read More

Cyclosporin A (CsA) is a fungal metabolite that has immunomodulatory and anti-inflammatory effects. Cyclosporin binds to cyclophilin, inhibiting CD4-T-cell activation. In this paper we discuss the mechanism of action of CsA and its role as a novel approach for the treatment of allergic disease.

Defects in mitochondrial function cause serious pediatric morbidity and mortality. Most mitochondrial disorders are caused by nuclear gene defects. To overcome the limitations of viral vectors for delivering gene products to mitochondria, we used protein transfection domains that cross cell membranes to deliver proteins expressed by nuclear genes to mitochondria.

Tuberculosis represents the main cause of mortality due to a single pathogen infection. Advances in anti-tuberculosis therapies are urgently required both for treatment of the 8-12 million new cases of tuberculosis leading to 2 million deaths each year, as well as for the 2 billion individuals already infected with M. tuberculosis, who are at the risk of developing disease. The present review summarizes the actually available in Read More

Natural polyphenolic compounds have attractive consideration for their cancer preventive effect. As their anti-cancer effect, inhibitory effect on angiogenesis would be important. Recently, it has been shown that quercetin has anti-angiogenic activity and is a potent anti-cancer agent. However, the activity of its glycosylated forms and related derivatives has not been investigated yet. In this study, we examined the effe Read More

The synthesis, biochemical evaluation and molecular modelling of a series of esters based upon testosterone is described. The compounds were tested for human placental aromatase (AR) inhibition in vitro and were found, in general, to be weaker than the standard non-steroidal compound, aminoglutethimide (AG), however, one compound [testosterone 4-nitrobenzoate (15)] was found be some six times more potent than A Read More

Osteoporosis, a common complex disease determined by multiple genetic, environmental and lifestyle factors, is mainly characterised by low bone density, leading to increased risk of low trauma fractures. Genetic factors play an important role in the etiopathogenesis of osteoporosis and may also influence its treatment. It is hoped that the ever-increasing genetics / genomics knowledge and techniques will greatly advance the Read More

Different mouse models have been generated to understand the molecular mechanisms involved in human tumorigenesis. Some of these models are produced by gene-targeting procedures, whereas others use the normal mouse as an experimental animal. The pathogenetic relevance of these mouse models has generated optimism for the development of effective targeted therapies, advances in rational drug design and Read More

Conjugates containing nigrin b (two-chain RIP) linked to a new lectin (SELld) from Sambucus ebulus L. have been designed. They retain the anti-ribosomal inhibitory activity of nigrin b but, in contrast to nigrin b, they exerted strong cytotoxicity on COLO 320 and HeLa cells, which ran in parallel with DNA fragmentation.

Discoid lupus erythematosus (DLE) is a skin disorder characterised by an active inflammatory phase that leads to the formation of atrophic scars. The molecular basis underlying the development of atrophic scars is not yet known. In this study we investigated the expression of the extra-cellular matrix (ECM) components of the BM, Laminin-1 (Ln-1), Laminin-5 (Ln-5), Collagen IV (Coll IV) and the expression of their integrin Read More

Pharmacophore hypotheses were generated for a series of isoxazolylpiperazine inhibitors selectively acting on the dopamine D4 receptor. HypoGen and HipHop programs in the CATALYST software were used to get insight into the structural features required for the inhibition activity. The HypoGen-generated pharmacophore model, with four features, which include HBAl, HBAl, HpAr, RA, showed high correlation (r = 0.950) Read More

The aim of the study was to investigate the effect of fenofibrate on the concentration and relative distribution of low density lipoprotein (LDL) subfractions in patients with combined dyslipidemia. Micronised fenofibrate was administered in a single daily dose of 200 mg. Serum lipid parameters and LDL subfraction concentrations were determined at baseline as well as after 16 weeks of treatment. Fenofibrate admini Read More

The naturally-occurring alkaloid ibogaine, found in the West African shrub Tabernanthe iboga, possesses the ability to diminish self-administration of substances of abuse, such as cocaine, heroin and alcohol. This was the lead structure for the design of a 16-member library of N-substituted isoquinuclidines. A solution-phase method for their synthesis is described.

Roxatidine acetate hydrochloride is a widely prescribed H2-receptor antagonist for peptic ulcers. Its conformation has been studied using 1H, 13C, and 15N NMR spectroscopy in DMSO-d6 and H2O:D2O (90:10) solvents coupled with AM1 calculations. The results show a folded conformation in DMSO-d6 as opposed to an extended structure in water. Its conformation in DMSO has been constructed with AM1 calculations and clos Read More