A series of new ceritinib analogs by extensive functionalization of the tail piperidine ring with various phosphamides and carbamates have been synthesized. All the ceritinib derivatives were evaluated for their cytotoxic activities against H2228 cell line. From the activity profile obtained, three of the tested compounds (compounds 4, 7 and 9) showed significant cytotoxic effects. Among these ...

Healthy volunteers received a single dose of gatifloxacin and moxifloxacin (400 mg each), and serum samples were obtained from these volunteers over a 24-h period. Prolonged (> or =12 h) serum bactericidal activity (SBA) was observed for both agents against staphylococcal isolates with minimum inhibitory concentrations (MICs) of gatifloxacin of < or =0.5 mug/mL. In strains with gatifloxacin MIC...

PARP-1 inhibition has been studied over the last decades for the treatment of various diseases. Despite the fact that several molecules act as PARP-1 inhibitors, a reduced number of compounds are used in clinical practice. To identify new compounds with a discriminatory PARP-1 inhibitory function, explicit-solvent molecular dynamics simulations using different inhibitors bound to the PARP-1 cat...

A new compound (1), named diaporthelactone, together with two known compounds (2 and 3) were isolated from the culture of Diaporthe sp., a marine fungus growing in the submerged rotten leaves of Kandelia candel in the mangrove nature conservation areas of Fugong, Fujian Province of China. The new compound was elucidated to be 1,3-dihydro-4-methoxy-7-methyl-3-oxo-5-isobenzofuran-carboxyaldehyde ...

it seems that rapid destruction of gram negative bacteria by antibiotics contributes to the clinical deterioration of some patients with gram negative infections. antibiotics increase the concentration of lipopolysaccharide (lps) in blood and cerebrospinal fluids. released lps can activate blood cells to produce tumor necrosis factor-alpha (tnf-a) and other cytokines. tnf-a appears to be a majo...

This study comprehensively investigated the influences of salinity, exposure concentration and time on the aggregate size, surface charge and dissolution of zinc oxide nanoparticles (ZnO-NPs; 20nm) in seawater, and examined the interacting effect of salinity and waterborne exposure of ZnO-NPs on the marine diatom Thalassiosira pseudonana for 96h. We found that aggregate sizes of ZnO-NPs signifi...

The rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new E(max) (maximum effect attributable to the drug) model was developed and further investigated in comparison with three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed. The rodent BATA data were obtained from a serie...

A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsi...

Reported are the in vitro susceptibilities of Plasmodium falciparum to artesunate, mefloquine, quinine and chloroquine of 86 isolates and to dihydroartemisinin of 45 isolates collected from areas of high resistance to mefloquine within Thailand near the borders with Myanmar and Cambodia, and from southern Thailand where P. falciparum is generally still sensitive to mefloquine. All the isolates ...

The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N-dibutylacetamido)-4-(1,3-benzodioxol-5- yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid (A-127722). This is a potent antagonist, binding to the ETA and ETB receptor subtypes...