Letters in Drug Design & Discovery - Volume 7, Issue 4, 2010

Here, we show that novel 2-aryl-3-(4-adamantyl-thiazol-21,3-thiazolidin-4-one derivatives have a mixed- or fully competitive mechanism of inhibition towards HIV-1 Reverse Transcriptase with respect to the substrates of the reaction. Thus, they are interesting starting points for the development of novel NNRTIs with an uncommon mechanism of action.

TRPV1 receptor is an important analgesia target. Its antagonists are expected to prevent pain perception by blocking the receptor directly. In this letter, eight dihydroisoquinoline-2(1H)-carbothioamide derivatives were designed and synthesized as TRPV1 antagonists. The benzene ring was modified with different substitutional groups. Preliminary biological tests suggested that the new compounds exhibited TRPV1 antagonist Read More

A series of novel 5-methyl-2,4-disubstitued-oxazole derivatives were synthesized and evaluated for their antitumor activities. The bioassay tests showed that 7-(5-methyl-2-(4-(R)phenyl)oxazol-4-yl)quinoline (R = trifluoromethyl, 2a; fluoro, 2b; chloro) and 2-(5-methyl-2-(4-(trifluoromethyl or fluoro)phenyl)oxazol-4-yl)pyrazine derivatives (4a and 4b) were highly effective against PC-3 cell with the IC50 values ranging from 1.2 t Read More

A new peptidic protease inhibitor (MpI) has been isolated from Maclura pomifera seeds, being the first trypsin and chymotrypsin inhibitor from a species belonging to the family Moraceae. MpI was purified by acetone precipitation, gel filtration and ion exchange chromatography, successively, with purification factors of 112 and 109 for the aforementioned enzymes, which are infrequent high values for inhibitors isolated from s Read More

A series of novel fluoroaminophosphates 4a-4j were synthesized by one-pot method in presence of tetramethylguanidine (TMG) as a catalyst and were characterized by elemental analysis, FTIR, 1H, 13C, 31P, 19F NMR, and mass spectra. All the title compounds were evaluated for in vitro cytotoxicity against leukemic cell line derived from Tcells of leukemia patient (CEM cells) by Trypan blue exclusion and MTT assays, and t Read More

New cholinesterase reactivators are synthesized as potential antidotes for treatment of organophosphorus agent poisonings or as part of pseudo catalytic scavengers for improvement of the nerve agent prophylaxis. In this study, three novel potential cholinesterase reactivators (K064 - (E)-1-(pyridinium)-4-(2-hydroxyiminomethylpyridinium)-but-2-ene dibromide; K065-(E)-1-(quinolinium)-4-(2-hydroxyiminomethylpyridinium)-bu Read More

3-Substituted isocoumarins 1-19 were synthesized and evaluated for their thymidine phosphorylase inhibitory activity. Eight (8) compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase from E. coli with IC50 values between 61- 402 iM. The activities were compared with the standard 7-deazaxanthine (IC50 = 39.28 ± 0.76 iM).

Thiomorpholine analogs (TML) have been identified as novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by MFA analysis has been performed to elucidate the atomic details of the TACE/TML interactions and to identify the most important features impacting TACE inhibitory activity of TMLs. The generated MFA model Read More

A series of seventeen disubstituted N-acylhydrazone pyrazinecarbohydrazide (4-20) have been synthesized and evaluated for their cell viabilities, were compared to another monosubstituted derivatives previously synthesized by us. This study indicated that the position and nature of the substituents in the aromatic ring influence the cytotoxicity of this series.

A novel sulfhydryl-β-D-glucose cholesterol 10a-10f as ligand for brain targeting liposomes was designed and synthesized. 10e was applied to the preparation of liposomal delivery system for achieving the brain-targeted delivery of the model drug tegafur in mice utilizing the glucose transporter member 1 (GLUT1). The results suggest the feasibility to enhance liposome's ability of delivering drug to brain by using the d Read More

The platelet-derived growth factor (PDGF-A, PDGF-B, PDGF-C, PDGF-D) family is composed of homo- and hetero-dimers that are potent mitogens for a wide variety of cell types. They exert their biological effects by binding to two receptor tyrosine kinases (α- and β-PDGFR). PDGF-AA, -AB, -BB and -CC dimers bind to the α-PDGFR with high affinity, whereas PDGF-BB and -DD dimers bind to β-PDGFR. Aberrant PDGF signaling lead Read More

The present work is a review of classical and recently developed methods for drop production in micro- and nanoencapsulation processes. Most of the methods and technologies used in microencapsulation processes require the formation of drops as a previous step. The drop formation step is very influential for the subsequent microparticle size and size distribution. These parameters, together with the microparticle structure, Read More