Letters in Drug Design & Discovery - Volume 2, Issue 5, 2005

The synthesis and some pharmacological properties of new symmetrical compounds are described. The cytotoxicity, apoptosis induction and caspase-3 activation of the synthesized compounds have been evaluated against three human cancer cell lines. Compounds that showed cytotoxic activity were tested as proapoptotic and caspase-3 activators. Some of the compounds showed interesting values as apoptosis inducers Read More

The taxane family of compounds has proven to be synthetically challenging targets. Using a novel [2+2] photocycloaddition reaction, several substituted cyclooctatrienes were synthesized and tested for tubulin polymerization activity. Elaboration of this methodology could allow the synthesis of a modified taxoid scaffold thereby permitting the efficient synthesis of paclitaxel analogs.

We identified a non-peptidomimetic HIV protease inhibitor sanguinarine through screening a small compound library with a high-throughput E. coli-based assay. In vitro, sanguinarine inhibits the HIV protease with an IC50 of around 13 μM. Based on docking results, binding modes of sanguinarine to the HIV protease are proposed.

The endogenous cannabinoids (endocannabinoids) are amides, esters and ethers of long chain polyunsaturated fatty acids. These lipids are bioactive signaling molecules that show diverse cellular and physiological effects and play various roles both in the central nervous system and in the periphery. The discovery of N-arachidonoylethanolamine (anandamide, AEA) and of the enzyme that terminates its signaling, i.e. fatt Read More

The binding of the indirubin analogue indirubin-3'-aminooxy-acetate (E243) to glycogen phosphorylase (GP) has been studied by kinetic and crystallographic experiments. E243 was shown to be a competitive inhibitor of GPb with respect to both Glc-1-P and AMP (Ki values of 21 ± 7 μM and 16 ± 3 μM, respectively). The crystal structure of the GPb-E243 complex determined at 1.9 Å resolution showed one ligand molecul Read More

Cyclooxygenase and 5-lipoxygenase pathways, which convert arachidonic acid into prostaglandins and leukotrienes, respectively, are the two major pro-inflammatory routes, whereas lipoxins, resolvins and neuroprotectins are potent endogenous anti-inflammatory mediators. Modulation of these pathways is key to control inflammation and to promote its resolution.

Animal models of diseases are essential for drug discovery and development. The availability of a large number of genetically-manipulated mice renders considerable interest in drug discovery by means of experimental models of disease. Ferric chloride-induced thrombosis is one of the most commonly used experimental models of thrombosis in mice. This review provides examples of optimizing this arterial thrombosis model Read More

This investigation was planned to assess the therapeutic efficacy of a novel designed nonsteroidal anti-inflammatory drug, M2000 (ß- D- mannuronic acid) in experimental models of rheumatoid arthritis, multiple sclerosis, glomerulonephritis, and nephrotic syndrome. The anti-inflammatory property of M2000 was tested in Adjuvant-induced arthritis (AIA) by intraperitoneal (i.p.) administration of 40 mg/Kg/day M Read More

A series of aromatic polycationic molecules were synthesised and tested as potential non-classical antiherpes agents. Analogue (4) had a high potency in all four of the HSV cell lines used and is far more potent than ribavirin. The fact that none of the new compounds show any selectivity for HSV-2 over HSV-1 may imply that there is no intervention of a HSV-2 glycoprotein C (gC) dependent pathway.