Search results for "structure-activity relationship"
showing 10 items of 743 documents
Marine Isonitriles and Their Related Compounds.
2016
Marine isonitriles represent the largest group of natural products carrying the remarkable isocyanide moiety. Together with marine isothiocyanates and formamides, which originate from the same biosynthetic pathways, they offer diverse biological activities and in spite of their exotic nature they may constitute potential lead structures for pharmaceutical development. Among other biological activities, several marine isonitriles show antimalarial, antitubercular, antifouling and antiplasmodial effects. In contrast to terrestrial isonitriles, which are mostly derived from α-amino acids, the vast majority of marine representatives are of terpenoid origin. An overview of all known marine isoni…
Decreasing the chlorophyll a/b ratio in reconstituted LHCII: Structural and functional consequences
1999
Trimeric (bT) and monomeric (bM) light-harvesting complex II (LHCII) with a chlorophyll a/b ratio of 0.03 were reconstituted from the apoprotein overexpressed in Escherichia coli. Chlorophyll/xanthophyll and chlorophyll/protein ratios of bT complexes and 'native' LHCII are rather similar, namely, 0.28 vs 0. 27 and 10.5 +/- 1.5 vs 12, respectively, indicating the replacement of most chlorophyll a molecules with chlorophyll b, leaving one chlorophyll a per trimeric complex. The LD spectrum of the bT complexes strongly suggests that the chlorophyll b molecules adopt orientations similar to those of the chlorophylls a that they replace. The circular dichroism (CD) spectra of bM and bT complexes…
Semiempirical PM5 molecular orbital study on chlorophylls and bacteriochlorophylls: Comparison of semiempirical,ab initio, and density functional res…
2003
The semiempirical PM5 method has been used to calculate fully optimized structures of magnesium-bacteriochlorin, magnesium-chlorin, magnesium-porphin, mesochlorophyll a, chlorophylls a, b, c(1), c(2), c(3), and d, and bacteriochlorophylls a, b, c, d, e, f, g, and h with all homologous structures. Hartree-Fock/6-31G* ab initio and density functional B3LYP/6-31G* methods were used to optimize structures of methyl chlorophyllide a, chlorophyll c(1), and methyl bacteriochlorophyllides a and c for comparison. Spectroscopic transition energies of the chromophores and their 1:1 or 1:2 solvent complexes were calculated with the Zindo/S CIS method. The self-consistent reaction field model was used t…
Quantitative structure-retention and retention-activity relationships of beta-blocking agents by micellar liquid chromatography.
2001
Abstract Sixteen β-blocking agents (acebutolol, alprenolol, atenolol, bisoprolol, carteolol, celiprolol, esmolol, labetalol, metoprolol, nadolol, oxprenolol, pindolol, practolol, propranolol, sotalol and timolol) showing a large range of hydrophobicity (octanol–water partition coefficients, log P between −0.026 and 2.81) were subjected to micellar liquid chromatography with sodium dodecyl sulfate as micelle forming agent, and n-propanol as organic modifier. The correlation between log P and the retention factor extrapolated to a mobile phase free of micelles and organic modifier was investigated. The use of an interpolated retention factor or the retention factor for specific individual exp…
Development of predictive retention-activity relationship models of non-steroidal anti-inflammatory drugs by micellar liquid chromatography: comparis…
2000
The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that under adequate experimental conditions the solute partitioning into chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis for drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict some biological activities of different kinds of drugs. In this study, quantitative retention-activity relationship (QRAR) models to describe som…
Biopartitioning micellar chromatography to pedict mutagenicity of aromatic amines
2007
[EN] Mutagenicity is a toxicity endpoint associated with the chronic exposure to chemicals. Aromatic amines have considerable industrial and environmental importance due to their widespread use in industry and their mutagenic capacity. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 in adequate experimental conditions, has demonstrated to be useful in mimicking the drug partitioning process into biological systems. In this paper, the usefulness of BMC for predicting mutagenicity of aromatic amines is demonstrated. A multiple linear regression (MLR) model based on BMC retention data is proposed and compared wi…
New benzothieno[3,2-d]-1,2,3-triazines with antiproliferative activity: synthesis, spectroscopic studies, and biological activity.
2014
New benzothieno[3,2-d]-1,2,3-triazines, together with precursors triazenylbenzo[b]thiophenes, were designed, synthesized and screened as anticancer agents. The structural features of these compounds prompted us to investigate their DNA binding capability through UV–vis absorption titrations, circular dichroism, and viscometry, pointing out the occurrence of groove-binding. The derivative 3-(4-methoxy-phenyl)benzothieno[3,2-d]-1,2,3-triazin-4(3H)-one showed the highest antiproliferative effect against HeLa cells and was also tested in cell cycle perturbation experiments. The obtained results assessed for the first time the anticancer activity of benzothieno[3,2-d]-1,2,3-triazine nucleus, and…
Binding of several phenothiazine neuroleptics to a common binding site of alpha 1-acid glycoprotein, orosomucoid.
1983
The interaction of several phenothiazine neuroleptics with alpha 1-acid glycoprotein was investigated using circular dichroism and equilibrium dialysis techniques. For chlorpromazine only, one high-affinity binding site of the protein was found. The binding of the drug to this single site generated typical polyphasic extrinsic Cotton effects. Since several other phenothiazine neuroleptics gave qualitatively comparable extrinsic Cotton effects in the presence of alpha 1-acid glycoprotein and potently inhibited the binding of chlorpromazine to the single site, it was concluded that all phenothiazine derivatives investigated bound preferentially to only one common binding site of the alpha 1-a…
Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives.
2014
STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growth factors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronic myelogenous leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently, literature reported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis in CML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5-inhibitory activity, two of them markedly more potent than pimozide.
SAR-studies of γ-secretase modulators with PPARγ-agonistic and 5-lipoxygenase-inhibitory activity for Alzheimer’s disease
2014
Abstract We present the design, synthesis and biological evaluation of compounds containing a 2-(benzylidene)hexanoic acid scaffold as multi-target directed γ-secretase-modulators. Broad structural variations were undertaken to elucidate the structure–activity-relationships at the 5-position of the aromatic core. Compound 13 showed the most potent activity profile with IC50 values of 0.79 μM (Aβ42), 0.3 μM (5-lipoxygenase) and an EC50 value of 4.64 μM for PPARγ-activation. This derivative is the first compound exhibiting low micromolar to nanomolar activities for these three targets. Combining γ-secretase-modulation, PPARγ-agonism and inhibition of 5-lipoxygenase in one compound could be a …