Medicinal Chemistry - Volume 1, Issue 2, 2005

The synthesis of C-12 deuterated and tritiated deoxoartemisinins is described. Tritiated deoxoartemisinin which could be incubated with the protein of Plasmodium falciparum for binding mechanism study was obtained by direct reduction of the carbonyl group of artemisinin using NaBT4 and BF3×Et2O in dried THF.

The membrane-embedded, ligand-gated P2X glycoprotein receptor is a monovalent-bivalent cation channel that is activated by physiological concentrations of extracellular ATP. A quantitative structure-activity relationship (QSAR) analysis was developed to model the cation permeability of the P2X2 channel and its mutants. As chemical properties, the helix-coil equilibrium constants and the distribution coefficients of the syst Read More

A novel series of 5-substituted-3-(1H-pyrrol-2-yl)-2-oxazolidinones 2a-s has been described as pyrrole analogues of toloxatone and befloxatone, two phenyl-oxazolidinones active as anti-MAO agents and used in antidepressant therapy. Tested against MAO-A and MAO-B enzymes, the majority of 2a-s show highly potent inhibitory effect against the A isoform of the enzyme, with Ki values in the range 0.52-0.004 μM, whilst their anti Read More

Recent advances in the design and preclinical evaluations of promising new generation taxane anticancer agents are reviewed in this article. Paclitaxel and docetaxel are two of the most important anticancer drugs today. However, recent reports have shown that treatment with these drugs often encounters undesirable side effects as well as drug resistance. Therefore, it is important to develop new taxane anticancer Read More

A metabolically stable and centrally acting analog of pGlu-Glu-Pro-NH2 ([Glu2]TRH, a tripeptide structurally related to TRH (thyrotropin-releasing hormone)) was designed by replacing the amino-terminal pyroglutamyl residue with a pyridinium moiety. The analeptic action of the analog was used to optimize the efficacy of this novel CNS agent when administered intravenously in its CNS-permeable prodrug forms obtained via Read More

Negatively charged gold nanoparticles featuring 2-(10-mercapto-decyl)-malonic acid were synthesized using the Murray place-displacement reaction. These water-soluble malonate gold mixed monolayer protected clusters (MMPCs) effectively bind and inhibit chymotrypsin based on complementary electrostatic surface recognition. The effect of increasing ionic strength on inhibition was also studied. It was observed t Read More

Six analogs of bidentate 1-[pyridoxylidene]-2-phenyl]hydrazine, twelve analogs of N2O-tridentate 1- [pyridoxylidene]-2-[heteroaryl]hydrazine, and four O2N-tridentate analogs of 1-[pyridoxylidene]-2-[heteroaroyl] hydrazines were synthesized and characterized. Their solutions in water and DMSO were assayed in vitro for activity against a chloroquine-resistant species of P. falciparum obtained from Hadassah Hospital Blood Read More

Quantitative Structure Activity Relationship (QSAR) techniques are used routinely by computational chemists in drug discovery and development to analyze datasets of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and Artificial Neural Networks (ANN) have been used on QSAR to establish correlations between molecular properties and bioactivity. However, ANN may be advantageous over PLS bec Read More

To clarify the biological role of the 90K/Mac-2BP glycoprotein, we evaluated the ability of two MAbs SP-2 and 1A4.22, to reveal this glycoprotein in both serum and tissue from hepatocellular carcinoma (HCC) patients. Tissue expression of 90K was detected by the immunohistochemical method in 20 HCC patients, while the 90K serum level was assessed by the ELISA assay in 13 HCC patients. MAb SP-2 was reactive only in serum, Read More

Cancer chemotherapy often fails due to acquired drug resistance. One of the most critical biochemical changes observed in drug-resistant tumor cells is over-expression of glutathione S-transferase Pi isozyme (GSTP1). Glutathione Stransferase inhibitors have been used as potentiating agents of chemotherapeutic drugs. Earlier we reported haloenol lactone 1 as a site-directed GSTP1 inactivator. We proposed that enzymatic hy Read More

The SELEX technique (systematic evolution of ligands by exponential enrichment) is a combinatorial library approach in which DNA or RNA molecules are selected by their ability to bind their protein targets with high affinity and specificity. The isolated molecules are referred to as aptamers (from aptus = Latin “to fit”). First, RNA and DNA aptamers were identified that bind to proteins naturally interacting with nuclei Read More