Medicinal Chemistry - Volume 5, Issue 3, 2009

Among the newer and promising weapons against cancer are Farnesyl Transferase Inhibitors (FTI). Indeed it is known that the enzyme Farnesyl Transferase (FT), catalyses the prenylation of cysteine residues of several proteins associated with cancer progression, including oncogenic forms of Ras.FTI could alter tumour progression. Exploration of our corporate structural database, based on concepts of diversity and similarit Read More

Imidazole and pyrrole-containing polyamides belong to an important class of compounds that can be designed to target specific DNA sequences, and they are potentially useful in applications of controlling gene expression. The extent of polyamide curvature is an important consideration when studying the ability of such compounds to bind in the minor groove of DNA. The current study investigates the importance of curvature Read More

The high mortality rate and lack of effective therapies make lung cancer an ideal target for novel therapeutic agents. The present study was designed to implement a novel chemical synthesis pathway and to determine the biological activities of synthetic makaluvamine analogs in human lung cancer. Seventeen compounds were synthesized and purified, and their chemical structures were elucidated on the basis of physic Read More

After administration of various amounts of pralidoxime to rats, the levels in serum, brain and cerebrospinal fluid (CSF) were measured using capillary zone electrophoresis (CZE). The calibration curves were established using spiked samples. The calibration covers the ranges from 0.3 - 200 μg/mL, 0.3 - 7 μg/mL and 0.1 - 7 μg/mL for serum, brain and CSF, respectively. The CZE measurement opens the way to the fast an Read More

To simulate new strategies for designing effective drugs against bird flu, we have carried out extensive studies by using various computer-aided drug design tools. Molecule AG7088 was first docked to the active site of H5N1 avian influenza neuraminidase (PBD code: 2HTY). The results thus obtained were compared with those by docking zanamivir (Relenza) and oseltamivir (Tamiflu) to the same receptor, respectively. It has b Read More

Dysfunction in α7 nicotinic acetylcholine receptor (nAChR), a member of the Cys-loop ligand-gated ion channel superfamily, is responsible for attentional and cognitive deficits in Alzheimer's disease (AD). To provide useful information for finding drug candidates for the treatment of AD, a study was carried out according to the following procedures. (1) DMXBA, a partial agonist of the α7 nAChR, was used as a template mol Read More

Cytochrome P450 2C9 (CYP2C9) is an important member of the cytochrome P450 enzyme superfamily with responsibility for metabolizing many important exogenous and endogenous compounds in many species of microorganisms, plants and animals. CYP2C9 is related to the oxidative of 16% of all therapeutics in current clinical use and has adverse drug effects, such as, enzyme induction and inhibition. In order to underst Read More

Antipsychotic medications have a diverse pharmacology with affinity for serotonergic, dopaminergic, adrenergic, histaminergic and cholinergic receptors. Their clinical use now also includes the treatment of mood disorders, thought to be mediated by serotonergic receptor activity. The aim of our study was to characterise the molecular properties of antipsychotic agents, and to develop a model that would indicate molecular Read More

We have previously shown the neuroprotective effect of atypical antipsychotic agents by experimental cerebral ischemia. However the impact of their high dose related side effects on their low dosage related neuroprotectivity is still unknown.We evaluated the possible neuroprotective effects of high dose olanzapine (10mg/kg) treatment on ischemic brain injury 24 hr after permanent cerebral ischemia. Olanzapine showed neit Read More

A series of 3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins with various 3-phenyl-2-propenoyl substituted groups at the 7β-position were synthesized, structurally characterized and evaluated for antibacterial activity in vitro. To prepare these derivatives by the Vilsmeier's reagent method, it was necessary to carefully control the reaction conditions in order to avoid the formation of the biological Read More

Febrifugine and its derivatives including halofuginone which possess very high activity against malaria were prepared synthetically from easily available starting material, 3-hydroxy picoline, and using simple reaction conditions. Synthesis of 2-amino-5, 6-methylenedioxy benzoic acid, (which is an intermediate for the process) is described. The selectivity enhancement in nitration of 3, 4-methylenedioxybenzaldehyde towards 6 Read More

Tacrolimus (FK506) is one of the immunosuppressive drugs used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variance in pharmacokinetics make it difficult to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters may influence tacrolimus exposure. A stepwise regression analysis was used to analyze t Read More