Search results for "Heterocyclic compound"

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resi…

2018

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Methods Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in bloo…

Scandium-44: Benefits of a Long-Lived PET Radionuclide Available from the 44Ti/44Sc Generator System

2011

(44)Ti/(44)Sc radionuclide generators are of interest for molecular imaging. The 3.97 hours half-life of (44)Sc and its high positron branching of 94.27% may stimulate the application of (44)Sc-labeled PET radiopharmaceuticals. This review describes the current status of (44)Ti production, (44)Ti/(44)Sc radionuclide generator development, post-processing of generator eluates towards medical application, identification of ligands adequate to Sc(III) co-ordination chemistry, proof-of-principle labeling of (44)Sc-DOTA-octreotides, investigation of in vitro and in vivo parameters, and initial applications for molecular imaging - both in small animals and humans.

Facile formation of a meso–meso linked porphyrin dimer catalyzed by a manganese(iv)–oxo porphyrin

2011

A manganese(IV)-oxo porphyrin catalyzes C-C bond formation between zinc porphyrins at the meso-position with a two-electron oxidant to afford the meso-meso linked porphyrin dimer efficiently. The meso-meso linked dimer is formed via formation of the porphyrin radical cation, and the rate-determining step in the catalytic cycle is the formation of a manganese(IV)-oxo porphyrin with a two-electron oxidant.

Epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole for six Candida species as determined by the colorimetric…

2013

ABSTRACT In the absence of clinical breakpoints (CBP), epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of susceptibility tests. Sensititre YeastOne (SYO) is a widely used method to determine susceptibility of Candida spp. to antifungal agents. The CLSI CBP have been established, but not for the SYO method. The ECVs for four azoles, obtained using MIC distributions determined by the SYO method, were calculated via five methods (three statistical methods and based on the MIC 50 and modal MIC). Respectively, the median ECVs (in mg/lit…

In vitro activity of linezolid, clarithromycin and moxifloxacin against clinical isolates of Mycobacterium kansasii

2005

To compare the activity of linezolid with a range of drugs used in the treatment of Mycobacterium kansasii infections.The percentages of resistant isolates against isoniazid, rifampicin and ethambutol were 2.9%, 1.9% and 2.9%, respectively. All isolates were susceptible to clarithromycin and moxifloxacin both with MIC(90) values of 0.125 mg/L. Linezolid was active against all isolates with MIC(50) and MIC(90) values of 0.5 and 1 mg/L, respectively, both below the susceptibility breakpoint established for mycobacteria.Linezolid, clarithromycin or moxifloxacin, could be used as alternative drugs for treatment of infections due to rifampicin-resistant isolates as well as short-course or interm…

A high-yielding modular access to the lamellarins: synthesis of lamellarin G trimethyl ether, lamellarin η and dihydrolamellarin η.

2013

Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones

2004

In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 v…

A Model of Smart G-Quadruplex Ligand

2012

An unprecedented strategy to control the quadruplex- vs duplex-DNA selectivity of a ligand is reported. We designed a compound whose structure can rearrange when it interacts with a G-quadruplex, thereby controlling its affinity. Thus, the first "smart G-quadruplex ligand" is reported, since this ligand experiences a structural change in the presence of quadruplexes but not in the presence of duplexes, ensuring a high level of quadruplex selectivity.

From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors

2007

In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38alphaMAPK IC50 of 1.8 muM. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38alpha- and JNK3-assay, whereas 5 was selective for p38alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compound…

G-quadruplex vs. duplex-DNA binding of nickel(II) and zinc(II) Schiff base complexes

2016

Novel nickel(II) (1) and zinc(II) (2) complexes of a Salen-like ligand, carrying a pyrimidine ring on the N,N' bridge, were synthesized and characterized. Their interaction with duplex and G-quadruplex DNA was investigated in aqueous solution through UV-visible absorption, circular dichroism and viscometry measurements. The results obtained point out that, while the zinc(II) complex does not interact with both duplex and G-quadruplex DNA, the nickel(II) complex 1 binds preferentially to G-quadruplex respect to duplex-DNA, with values of the DNA-binding constants, Kb, 2.6×10(5)M(-1) and 3.5×10(4)M(-1), respectively. Molecular dynamics simulations provided an atomic level model of the top-sta…