Letters in Drug Design & Discovery - Volume 1, Issue 3, 2004

The human immunodeficiency virus (HIV), a retrovirus, is known to cause the acquired immunodeficiency syndrome (AIDS) as the HIV infection develops. Efforts on searching new anti-HIV agents to provide effective treatment of HIV infection / AIDS have never been slowed down since the discovery of HIV. Nowadays a promising area of research has focused on preventing HIV entry into host cells, called entry inhibitors, whi Read More

We present the SAR study that led us to identification of the first inhibitors of type 7 17β- hydroxysteroid dehydrogenase (17β-HSD). The conversion of E1 into E2 is reduced by nearly 90 % by 17β-(Nalkylformamido)- 4-methyl-4-aza-5α-androstan-3-one compounds bearing a side chain containing 7 to 10 carbon atoms when tested at 0.3 μM.

Several 6H-indeno[1,2-c]isoquinolin-5,11-diones and 5H-dibenzo[c,h][1,6]naphthyridin-6-ones were synthesized and evaluated for their relative topoisomerase I-targeting activity and cytotoxicity. Comparative studies were performed in P388, RPMI8402, and U937 tumor cell lines, as well as their camptothecin-resistant variants, i.e. P388 / CPT45, CPT-K5, and U937 / CR, respectively. The relative cytotoxic activity of these com Read More

Peptide based vaccine design for cancer immunotherapy is currently being used in clinical trials for malignant melanoma with much success. Administration of synthetic peptides derived from proteins overexpressed in tumour cells (tumour-associated antigens) can elicit tumour-specific CD8+ T cell responses in vitro and in vivo. Currently, a number of tumour antigens from overexpressed cancer proteins such as mucin 1 Read More

Asthma has reached epidemic proportions with approximately 200 million individuals affected worldwide. The disease is characterized by an oxidant / antioxidant imbalance in the lungs leading to activation of redox-sensitive transcription factors e.g. activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B). We have previously described PNRI-299, a small molecule beta-strand mimetic template compound, as an Read More

Detailed SAR examination and DIStance COmparison (DISCO) computation were used for identification and superposition of common structural features of 2,3-benzodiazepines with high affinity to an allosteric AMPA binding site. Two similar 4-point models were identified; both contained 2 donor sites, a donor atom and a hydrophobic centre. At one of the donor sites a characteristic difference between the two models was observed.

Imidazopyridines and imidazopyrimidines have been prepared and tested for their antibacterial activity in vitro. Structure activity relationship studies indicate (SAR) that a modulation of both natures of arm in position 3 and atom in position 8 of these compounds has a direct impact on the antibacterial activity.

Antimicrobial peptides are essential components of the innate immunity of all animal species. These peptides have a broad range of activity against resistant microorganism strains primarily because of their distinct mechanisms of action. Several groups are currently developing synthetic and / or variant peptides as new therapeutic drugs against specific pathogens.

The proteome is described as the entirety of all proteins expressed within a cell at a given moment. In contrast to the stability of the genome, the proteome is highly dynamic and reflects the cell's current status. Since proteins carry out almost all biological functions, the proteome stands in direct relation to cellular functions. Proteomic analysis (i.e., two-dimensional electrophoresis, mass spectrometry and bioinformatics) ai Read More

Development of a water-soluble prodrug of doxorubicin-formaldehyde conjugate, a labile, active metabolite of doxorubicin, is described. The lead compound is the doxorubicin-salicylamide N-Mannich base, N-(2-hydroxybenzamidomethyl)-doxorubicin (doxsaliform), prepared in 72% yield from reaction of salicylamide with doxorubicin in the presence of formaldehyde. Doxsaliform releases doxorubicin-formaldehyde conjugate u Read More

A novel gene modulation system was identified within mammalian introns, regulating intracellular gene transcripts homologous to certain 5'-proximal non-snRNP-binding regions of spliced introns. This gene modulation system can be manipulated for the analysis of gene function and development of gene-specific therapeutics, using artificial introns with 5'-proximal hairpin inserts.

Apoptosis plays a major role in homeostasis as well as proliferation and differentiation. The important role of epithelial and endothelial cell apoptosis in lung injury and repair has been demonstrated. Modulating signaling molecules of apoptosis may be effective treatment against lung injury.

Atorvastatin therapy (20 mg / day given for 2 months) to hypercholesterolemic patients resulted in a reduction, by 59%, in their human monocyte-derived macrophages (HMDM) cholesterol content. The macrophage lipid peroxides content, and cell-mediated oxidation of LDL were reduced by 25% and 48% after atorvastatin therapy, as compared to the patients' macrophages before therapy. This therapy increased paraoxonas Read More

The stereospecific synthesis of nine trans-combretastatin analogs (5 - 13) is described. The trans geometry of these products was ascertained by the vinylenic proton NMR coupling constants of 15 - 16 Hz, and also by a single crystal x-ray structure of the tetramethoxy compound 6. Continuous 3-day exposure of murine B16 melanoma cells to the trans-combretastatin analogs 5 - 13 showed that two of the analogs (2 and 4) had Read More

Ischaemic diseases, a major public health problem worldwide, are associated with a decrease in oxygen supply to mitochondria that impairs respiration, energy production and constitute stimuli for cell death. This paper summarises the pharmacological strategies targeting the mitochondrial respiratory chain, which represents an interesting therapeutic perspective.

The thioxylation of the potent Neurokinin A antagonist MEN 10627 by Lawesson's reagent showed to be potentially useful for the post-synthetic manipulation of the related family of structurally peculiar bicyclic hexapeptides, whose synthesis in combinatorial manner has been recently described.

Rabies, a viral zoonosis is usually transmitted to humans through the bite of an infected animal. In many parts of the world, predominantly developing countries human rabies is still a disease of significant public health concern. Rabies also less frequently afflicts humans in the developed world, most cases occurring as the result of exposure to infected wild animals, especially rabid bats. Therapy administered following the Read More