Letters in Drug Design & Discovery - Volume 2, Issue 4, 2005

These diterpenes (1) and (2) were synthesized via epoxidation and rearrangements of (-)-Kaur-9(11), 16-dien-19-oate (7) isolated from Venezuelan species of espeletia (frailejon), and their antimicrobial and antitumoral activity were evaluated. Compound (1) showed GI50 values of 51.6 nM against CNS SF-539, LC50 = 100 μM, log10 GI50 = -7.29; compound (2) showed GI50 at 4.17 μM against breast cancer T47D, LC50 = 39 Read More

The synthesis of two antineoplastic compounds is accomplished by placing threemethanesulfonate groups on folic acid (I) and triethanolamine (II). Methane-sulfonate agents (I) and (II), alkylate an aqueous nucleophilic primary amine group at physiological pH 7.4 and 37 °C. Compound (I) utilizes folic acid as a drug carrier for highly specific delivery into tumor cells that have increased folic acid receptors. There are three reactive Read More

Primary or secondary resistance towards conventional chemotherapeutic agents presents the major clinical obstacle in the induction of remission and definite cure of hematological malignancies. Definition of the underlying molecular mechanisms determining response or resistance not only enables the clinician to define prognostic markers, but moreover, facilitates the design of molecularly targeted therapies aiming to reve Read More

The deregulated cell cycle is a prominent hallmark of oncogenesis. In addition to the genetic alterations in G1 and S phase, emerging data demonstrate that the loss of checkpoint control at the G2/M transition is also closely involved in neoplastic transformation. Among many modulators of the G2/M transition, the defective regulation of cyclin B1, the regulatory subunit of cyclin dependent kinase 1 (Cdk1), and Read More

Hydralazine is a drug used as anti-hypertensive, and recently reported to be a DNA methylation inhibitor able to demethylate and reactivate the expression of tumor suppressor genes in cancer. The aim of the present study was to explore the potential mechanism by which hydralazine inhibits DNA methylation. For this purpose, we assessed the structural and electronic properties between 1-hydrazinophthalazine (hydral Read More

A quantitative structure-activity relationship (QSAR) study is made on a series of Na+ channel blockers (diphenylacetamide derivatives) and on a series of K+ channel blockers (blockers of cardiac delayed rectifier potassium current IKs) (benzodiazepine derivatives). In both the cases, the blocking activity is found to be significantly correlated with Kier's first-order valence molecular connectivity index.

A bicyclic spiro analogue of D-proline was synthesized from perbenzylated methyl D-fructoside. The synthetic steps required first a three carbon chain elongation at the anomeric position by C-glycosylation, secondly the introduction of the amino function at C-1, and finally the cyclization to the pyrrolidine ring and introduction of the carboxylic group.

In order to gain inside the mechanism of action of a series of benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives with in vitro anti-trypanosomal activity, electrochemical and biological studies were performed. Cyclic voltammetry and electron spin resonance spectroscopy were used to predict the bio-reduction processes. Effects on the parasitic respiration were studied.

A novel series of nonradiolabeled, polyfluorinated phenyltropanes were developed containing three or more 19 F atoms/molecule in a magnetic resonance (MR) equivalent chemical environment to increase coherent MR signal characteristics. Competitive radioreceptor affinity assays of such compounds yielded nM affinity at dopamine (DAT) and serotonin (SERT) transporters in rat brain tissue. Compound 3b (MCL-314) at 50 μ Read More

The title compounds have been synthesized and tested for structure activity relationship for Phospholipase A2 (PLA2) [E.C. 3.1.1.4] enzyme inhibition. The in vitro PLA2 enzyme inhibitory activity of azetidin-2-one derivatives and in vivo anti-inflammatory activity studies using mice are highlighted. The results show that some azetidin-2-one derivatives are very good PLA2 inhibitors and can also be used as antiinflammatory drugs.

The present study summarizes results obtained with PACAP treatment in models of neurodegenerative diseases. The data show that PACAP protected a significant number of neurons in quinolinic acid- and 6-hydoxydopamine-induced lesions, which correlated with the less severe behavioral symptoms. These effects may have clinical implications in Huntington and Parkinson's diseases.

Recently, it has been emphasized that oxidative stress could play a synergistic role with tau phosphorylation, cell shape changes, cytoskeletal disruption and cell death in Alzheimer's disease. Okadaic acid induces oxidative damage, cell shape alterations, tau hyperphosphorylation and cytoskeletal disorganization similar to Alzheimer's disease. In this sense, different evidence suggests that indolamines may be useful for Read More

Ab initio molecular orbital calculations are employed to elucidate structural and electronic characteristics of a series of eicosanoids, which have been used to examine the specificity of a 14,15-DHET ELISA. The results of the calculations show that activity is correlated to two combined factors: molecular volume and energy of the HOMO.

A number of novel 1,5-diarylpyrazoles possessing N-substitution on the sulfonamide (-SO2NH2) moiety were synthesized and tested for COX-1/COX-2 inhibition in vitro. Many of these 1,1-dioxo-2,3- dihydrobenzo[d]isothiazolyl substituted 1,5-diarylpyrazoles, where the SO2NH2 group was a part of the fused ring, showed COX inhibitory activity. Few of them were identified as selective COX-2 inhibitors. Structure Activity Relationship st Read More