Search results for "IC50"
showing 9 items of 129 documents
ChemInform Abstract: Synthesis and Antiproliferative Activity of Novel 3-(Indazol-3-yl)-quinazolin-4(3H)-one and 3-(Indazol-3-yl)-benzotriazin-4(3H)-…
2010
Several new 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives 5 and 6 were synthesized and tested for their in vitro antiproliferative activity against Raji, K562, and K562-R cell lines. The pharmacological screening showed that some 2, 6, or 7-substituted quinazolinones 5 posses a significant antiproliferative activity, with a percentage growth inhibition ranging from 44.8% to 100% at 50 microM, which was higher than that showed by the unsubstituted derivative 5a previously synthesized. For the most active compounds 5d, 5f, and 5g the IC50 were recorded.
ChemInform Abstract: Synthesis of New 3-(3-Phenyl-isoxazol-5-yl) or 3-[(3-Phenyl-isoxazol-5-yl)amino] Substituted 4(3H)-Quinazolinone Derivatives wit…
2010
A novel series of 3-(3-phenyl-isoxazol-5-yl) or 3-[(3-phenyl-isoxazol-5-yl)amino] substituted 4(3H)-quinazolinone derivatives was synthesized. The compounds were tested for their antineoplastic activity in vitro against Raji (human Burkitt limphoma). K-562 (human chronic myelogeneous leukemia) and U937 (human histiocytic limphoma) cell lines. The most active quinazolinones showed IC50 values in the range 16-30 microM.
Cytotoxic effects of individual and combined sterigmatocystin and nivalenol on liver hepatocellular carcinoma cells
2020
Abstract Since humans are exposed to different mycotoxins through daily intake, there is increasing concern about the adverse effects of the interactions between them. Cytotoxicity of sterigmatocystin (STE) and nivalenol (NIV) alone and in combination in human hepatocarcinoma (HepG2) cells was evaluated by MTT assay. Furthermore, ROS production and alteration of ΔΨm as mechanisms of action were assessed. Cells were treated with concentrations ranging from 0.15 to 5 μM for NIV and from 0.78 to 50 μM for STE individually and in binary combinations. The combination ratio between the mixture STE + NIV was 10:1. The IC50 values of NIV ranged from 0.96 to 0.66 μM, whereas no IC50 values were obta…
Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles, Analogues of the Marine Alkaloid Nortopsentin
2013
2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.
Diminished Inhibition of Adhesion Molecule Expression in Prostacyclin Receptor Desensitized Human Platelets
1995
Long-term exposure of platelets to prostacyclin or iloprost (100nM, 3hr) results in receptor desensitization measured as decrease in 3H-iloprost binding sites by 47 +/- 14%. Desensitized platelets respond with an increased adhesion to endothelial cells. The mechanism of increased adhesiveness was studied by measuring the expression of the adhesion molecule CD62p (p-selectin; GMP140) on washed human platelets by flowcytometry. In thrombin stimulated platelets CD62p expression was dose-dependently reduced by iloprost. In receptor desensitized platelets IC50 for iloprost inhibition of thrombin-induced CD62p expression increased from 0.48 +/- 0.10 to 2.4 +/- 0.7 nM.
Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repagl…
2004
The 11 C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-(( 11 C)methoxy)-4-(3-methyl-1-(2-piperidine-1-yl-phenyl)- butyl-carbamoyl)-benzoic acid (( 11 C)methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic b-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/lmol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induce…
Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors
2016
Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar to a low-micromolar value for the most active rhodesain inhibitor (R,S,S)-3. All compounds showed a good selectivity against the target enzyme since all of them were proven to be poor inhibitors of human cathepsin L. Novel rhodesain inhibitors were developed by combining an enantiomeri…
Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and rela…
2016
A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compo…
Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action
2015
Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition…