Search results for "Structure–activity relationship"
showing 10 items of 290 documents
Modeling anti-allergic natural compounds by molecular topology.
2013
Molecular topology has been applied to the search of QSAR models able to identify the anti-allergic activity of a wide group of heterogeneous compounds. Through the linear discriminant analysis and artificial neural networks, correct classification percentages above 85% for both the training set and the test set have been obtained. After carrying out a virtual screening with a natural product library, about thirty compounds with theoretical anti-allergic activity have been selected. Among them, hesperidin, naringin, salinomycin, sorbitol, curcumol, myricitrin, diosmin and kinetin stand out. Some of these compounds have already been referenced as having anti-allergic activity.
In silicoAntibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach
2015
In the recent times, the race to cope with the increasing multidrug resistance of pathogenic bacteria has lost much of its momentum and health professionals are grasping for solutions to deal with the unprecedented resistance levels. As a result, there is an urgent need for a concerted effort towards the development of new antimicrobial drugs to stay ahead in the fight against the ever adapting bacteria. In the present report, antibacterial classification functions (models) based on the topological molecular computational design-computer aided >rational> drug design (TOMOCOMD-CARDD) atom-based non-stochastic and stochastic bilinear indices are presented. These models were built using the li…
Retention pharmacokinetic and pharmacodynamic parameter relationships of antihistamine drugs using biopartitioning micellar chromatography
2001
Abstract Antihistamines are drugs which act by competitive inhibition of the H1 or H2 histamine receptors. Little has been known about their clinical pharmacokinetics and biological responses until the last few years. In this paper, we propose quantitative retention–activity relationship, QRAR, models based on the retention data of antihistamines in a biopartitioning micellar chromatography (BMC) system using a Brij35 mobile phase for describing pharmacokinetic parameters such as half-life and volume of distribution, or the pharmacodynamic parameters, therapeutic plasma levels, lethal doses and drug-receptor dissociation constant. The predictive ability of these models is statistically vali…
Synthesis and antiproliferative activity of the ring system [1,2]oxazolo[4,5-g]indole.
2012
Brand new ring: A series of 27 derivatives of the new ring system [1,2]oxazolo[4,5-g]indole were conveniently prepared and tested at the NCI for antiproliferative studies. Several of them showed good inhibitory activity toward all tested cell lines, reaching GI50 values generally at the micromolar and sub-micromolar levels and in some cases at nanomolar concentrations. The mean GI50 values, calculated on the full panel, were in the range 0.25-7.08 μM.
1-methil-3H-pyrazolo[1-2-a]benzo[1-2-3-4]tetrazin-3-ones, design synthesis and biological activity of new antitumoral agents
2005
1-Methylpyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones 4, synthesized in good to excellent yields, were designed as novel alkylating agents because of their peculiar chemical behavior. All derivatives showed antiproliferative activity against more than 50 types of tumor cell lines with GI50 reaching sub-micromolar values. SAR studies revealed that the presence of a chlorine atom is well-tolerated in both positions 8 and 9, whereas in the case of the methyl group, switching from the 8 to the 9 position gives rise to the most active compound of the series, 4g, either for the number of cell lines inhibited and for selectivity against leukaemia and renal cancer subpanels. COMPARE and 3D-MIND comp…
A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.
2012
In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…
Flavanones in Citrus fruit: structure-antioxidant activity relationships
2005
Epidemiological surveys have shown an inverse relationship between the intake of fruit and the incidence of coronary heart disease and some type of cancer. Data found in the literature regarding the flavonoids in general while this study focuses on flavanones, a subclass of flavonoids which occurs in Citrus fruit. The aim of this work is to elucidate the antioxidant or pro-oxidant behaviours of some common flavanones and to determine their activity–structure relationships as antioxidant using the crocin bleaching inhibition assay. The compounds studied were regarding both the aglycon form and the glycoside form. Data evidence that the substitution of the 7th OH group of the flavanones by a …
Nonsteroidal Antiinflammatory Agents, XVIII: C-5 Functionalized 6,7-Diphenyl-2,3-dihydro-1H-pyrrolizines as Inhibitors of Bovine Cyclooxygenase and 5…
1994
6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding pro…
Biopartitioning micellar chromatography: An alternative high-throughput method for assessing the ecotoxicity of anilines and phenols
2007
An investigation of the use of the chromatographic retention (log k) as an in vitro approach for modelling the toxicity to Fathead Minnows of anilines and phenols is developed. A data set of 65 compounds with available experimental toxicity data was used. Log k data at three pH values were used for the compounds classification and two groups or 'MODEs' were identified. For one 'MODE' a quantitative retention-activity relationship (QRAR) model was calculated. Finally, it was used to estimate the toxicity to Fathead minnows of anilines and phenols for which experimental data are not available. These estimations were compared to those obtained from another toxicity (to Tetrahymena pyriformis) …
Herbicidally Active Derivatives of Aminomethylenebis-Phosphonic Acid-Mode of Action and Structure - Activity Relationship
1996
Abstract: (N-pyridylamino)methylenebisphosphonates exhibit strong herbicidal activity which may be reversed by supplementation of the growth media with aromatic amino acids. They appeare to be the inhibitors of aromatic amino acids biosynthesis acting as inhibitors of DAHP synthase the first enzyme of shikimate pathway. Over 40 analogues of these acids were synthesized in order to determine the structure-activity relationship.