Letters in Drug Design & Discovery - Volume 11, Issue 6, 2014

In this work the use of 2D atom-based quadratic indices is shown in the prediction of proteasome inhibition. Machine learning approaches such as support vector machine, artificial neural network, random forest and k-nearest neighbor were used as main techniques to carry out two quantitative structure-activity relationship (QSAR) studies. First, a database consisting of active and non-active classes was predicted wit Read More

In the present study, a series of novel quinazolinones functionalized with urea/thiourea/thiazole derivatives was synthesized and evaluated for their antioxidant and 5-lipoxygenase (5-LOX) inhibition activities. The newly synthesized compounds were characterized using 1H NMR, 13C NMR, IR, Mass spectra and elemental analysis. The antioxidant activities of the title compounds were evaluated using DPPH, superoxide, hydroxyl Read More

Soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators which are involved in the regulation of blood pressure and inflammation. Although the most reported potent sEH inhibitors are urea derivatives, these compounds have limited pharmacokinetic profile. In order to improve physicochemical properties, besides having favorable potency, amide non-urea deri Read More

The development of antitumor drugs with novel effects is urgent for cancer patients. In our recent anticancer drug discovery study, 1,2-di(quinazolin-4-yl)diselane (LG003) was synthesized and showed considerable antitumor effects on six tested cancer cell lines in vitro. Morphological observation and Lactate Dehydrogenase release assay revealed that LG003 exerted such effect in A549 cells through antiproliferation, a Read More

A series of aryl benzyl ethers with fluoro substituents were synthesized and their structures were confirmed by spectral. All the compounds were tested for their cytotoxic activity in vitro against two human tumor cell lines: A549, SGC7901, and most showed cytotoxicity. Compound 10 was the most active in suppressing the growth of both screened cancer cells.

Four naphthalimide derivatives 2-5 modified with various alkylenediamines at 4-position have been designed and synthesized. Their anticancer activities were preliminarily evaluated, which showed potent anticancer activities against A549 cell line with IC50 values lower than 5 μM. Furthermore, the DNA binding properties of 2 with calf thymus (Ct) DNA were investigated by UV-Vis, fluorescence, and circular dichrois Read More

Adenosine deaminase (ADA) inhibitors have been found to have antitumor activities. Here, thirteen potential adenosine deaminase inhibitors 5-amino-1H-pyrazole-4-carboxamide derivatives were designed, synthesized and screened for antitumor activities. Compound 8e exhibited strong growth-inhibitory effects which showed selectivity toward the estrogen receptor positive breast cancer cells (MCF-7) compared to other Read More

A simple and facile route has been described for the synthesis of macrocyclic tetraamides. This method is applicable for the preparation of a variety of macrocyclic tetraamides of various heteroatom substitutions.

A series of N1-substituted 2,4,5-triphenyl imidazole derivatives was designed, synthesized and evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferative activities in vitro against four human cancer cell lines (PC3, KB, A549 and HCT116). Although logical evaluation revealed weak p53-MDM2 binding inhibitory activities, most of the obtained molecules displayed moderate to potent cytotoxicities again Read More

2,5-[[(1,1-Dimethylethyl)oxidoimino]methyl]-3,6-trimethylpyrazine (TN-2), a novel derivative of tetramethylpyrazine (TMP), is effective in reducing brain infarct size in animal brain ischemia models. The purpose of this study is to evaluate its pharmacokinetic profiles including plasma pharmacokinetics, dose proportionality, tissue distribution, excretion in rats and protein binding ability in vitro. In doses ranging from 5 t Read More

Adenosine 5’-monophosphate (AMP) activated protein kinase (AMPK) is a highly conserved sensor of cellular energy. AMPK has been recognized as a key regulator of mammalian metabolic function and has emerged as an attractive target for the treatment of metabolic disorders, including obesity and type 2 diabetes. The synthesis and biological evaluation of novel 3-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)propanoic acid deri Read More

The rationale of this study was to investigate the effect of cyclodextrins (β-CD or HPβ-CD) on the dissolution of a poorly water soluble drug: Piroxicam (Px). Interactions of piroxicam (Px) and β-CD or hydroxypropyl-β-CD (HPβ- CD) have been investigated in solution and in the solid state. The phase solubility of inclusion complex for each CD was studied according to Higuchi and Connors method. Equimolecular (Px - β-CD) Read More

Induced fit docking approach was utilized to decipher the binding mode of the recently reported dibenz[b,f]1,5- oxazocine derivative having activity towards κ -Opioid receptor. The result of docking to newly resolved crystallographic structure of κ -Opioid receptor established the important interactions as two hydrogen bonds, a π-π interaction, and two hydrophobic interactions. Based on the study it is inferred that protonate Read More

In this study, we aimed at the synthesis of new 2-((5-substituted-4-methylthiazol-2-yl)amino)-2-oxoethyl 4- substitutedpiperazine-1-carbodithioate derivatives and their antibacterial, antifungal, antioxidant and AChE inhibitory evaluations. A set of fifteen new compounds of 2-((5-substituted-4-methylthiazol-2-yl)amino)-2-oxoethyl 4-substitutedpiperazine- 1-carbodithioate derivatives were synthesised by reacting 2-chloro-N-(5-s Read More