Search results for "structure-activity relationship"
showing 10 items of 743 documents
Structural considerations on the iridoids as anti-inflammatory agents.
1994
Abstract Twelve iridoid glycosides have been evaluated for their anti-inflammatory activity on two models: the carrageenan-induced mouse paw edema and the TPA-induced mouse ear edema. Loganic acid was the most active (44.4% edema inhibition) on the former test, whereas the catalpol derivative mixture isolated from Scrophularia, aucubin, verbenalin, and loganin, showed the highest activity (from 72.0 to 80.0% edema inhibition) on the latter. The results allowed us to establish the relationship between the structure and anti-inflammatory activity on the basis of the different patterns of substitution, particularly hydroxylation, unsaturation, and acylation.
Potential Antipsoriatic Avarol Derivatives as Antioxidants and Inhibitors of PGE2 Generation and Proliferation in the HaCaT Cell Line
2004
The synthesis and structure-activity relationships for a series of 14 new avarol derivatives as antioxidants and inhibitors of cell proliferation and PGE(2) generation in human keratinocytes are described. Compound 6 (thiosalicylic derivative) was the most potent inhibitor of superoxide generation in human neutrophils and also potently inhibited PGE(2) generation in the human keratinocyte HaCaT cell line. Compound 7(3'-methylaminoavarone) presented the best antiproliferative profile, by the inhibition of (3)H-thymidine incorporation in HaCaT cells, with potency similar to the reference compound anthralin. None of the avarol derivatives showed any sign of cytotoxicity measured as LDH release…
Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives
2011
Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar conc…
Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment.
2020
In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure-activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.
Relation between structural and release properties in a polysaccharide gel system.
2007
Abstract The potential utility of κ-carrageenan gels for preparing drug release devices is here shown. Structural properties of κ-carrageenan gels prepared with different salt composition and containing Ketoprofen sodium salt, as model drug, have been evaluated with static light scattering and rheological measurements. These properties have been correlated with release profiles in vitro at pH 5.5. Release properties from gelled matrices have been compared with those obtained by two commercial products containing the same drug. Results show that: i) in this system it is possible to easily control the gel texture by using different cationic concentration; ii) the kinetics of drug release by κ…
Structure–activity relationships, and drug metabolism and pharmacokinetic properties for indazole piperazine and indazole piperidine inhibitors of RO…
2007
ROCK has been implicated in many diseases ranging from glaucoma to spinal cord injury and is therefore an important target for therapeutic intervention. In this study, we have designed a series of 1-(4-(1H-indazol-5-yl)piperazin-1-yl)-2-hydroxy(or 2-amino) analogs and a series of 1-(4-(1H-indazol-5-yl amino)piperidin-1-yl)-2-hydroxy(or 2-amino) inhibitors of ROCK-II. SR-1459 has IC50 = 13 nM versus ROCK-II while the IC50s for SR-715 and SR-899 are 80 nM and 100 nM, respectively. Many of these inhibitors, especially the 2-amino substituted analogs for both series, are modest/potent CYP3A4 inhibitors as well. However, a few of these inhibitors (SR-715 and SR-899) show strong selectivity for R…
Resveratrol-Related Dehydrodimers: Laccase-Mediated Biomimetic Synthesis and Antiproliferative Activity
2012
Seven resveratrol-related monomeric stilbenoids were submitted to biomimetic oxidative coupling in the presence of laccase from Trametes versicolor (TvL), and gave racemic dihydrobenzofuran dehydrodimers (±)-15 to (±)-21. These products, after spectral characterization, were submitted to an antiproliferative activity bioassay against SW480 human colon cancer cells. Five racemates were found to be active, and were resolved by chiral HPLC. The pure enantiomers were subjected to circular dichroism measurements to establish their absolute configurations at C-7 and C-8. These enantiomerically pure compounds were submitted to the antiproliferative activity assay towards SW480 cells, and were all …
Molecular dynamics, dynamic site mapping, and highthroughput virtual screening on leptin and the Ob receptor as anti-obesity target.
2014
Body weight control is a mechanism finely regulated by several hormonal, metabolic, and nervous pathways. The leptin receptor (Ob-R) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream, and under normal circumstances, circulating levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased concentrations lead to opposite effects. Therefore rational design of leptin agonists constitute an appealing challenge in the battle against ob…
Discovery of novel anti-inflammatory drug-like compounds by aligning in silico and in vivo screening: The nitroindazolinone chemotype
2011
In this report, we propose the combination of computational methods and in vivo primary screening in zebrafish larvae and confirmatory in mice models as a novel strategy to accelerate anti-inflammatory drug discovery. Initially, a database of 1213 organic chemicals with great structural variability - 587 of them anti-inflammatory agents plus 626 compounds with other clinical uses - was divided into training and test groups. Atom-based quadratic indices - a TOMOCOMD-CARDD molecular descriptors family - and linear discriminant analysis (LDA) were used to develop a total of 13 models to describe the anti-inflammatory activity. The best model (Eq. (13)) shows an accuracy of 87.70% in the traini…
Excitation-Wavelength-Dependent Photocycle Initiation Dynamics Resolve Heterogeneity in the Photoactive Yellow Protein from Halorhodospira halophila
2018
Photoactive yellow proteins (PYPs) make up a diverse class of blue-light-absorbing bacterial photoreceptors. Electronic excitation of the p-coumaric acid chromophore covalently bound within PYP results in triphasic quenching kinetics; however, the molecular basis of this behavior remains unresolved. Here we explore this question by examining the excitation-wavelength dependence of the photodynamics of the PYP from Halorhodospira halophila via a combined experimental and computational approach. The fluorescence quantum yield, steady-state fluorescence emission maximum, and cryotrapping spectra are demonstrated to depend on excitation wavelength. We also compare the femtosecond photodynamics …