Search results for "structure-activity"
showing 10 items of 746 documents
Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity.
2003
A topological virtual screening (tvs) test is presented, which is capable of identifying new drug leaders with anticonvulsant activity. Molecular structures of both anticonvulsant-active and non active compounds, extracted from the Merck Index database, were represented using topological indexes. By means of the application of a linear discriminant analysis to both sets of structures, a topological anticonvulsant model (tam) was obtained, which defines a connectivity function. On the basis of this model, 41 new structures with anticonvulsant activity have been identified by a topological virtual screening.
Applying pattern recognition methods plus quantum and physico-chemical molecular descriptors to analyze the anabolic activity of structurally diverse…
2008
The great cost associated with the development of new anabolic-androgenic steroid (AASs) makes necessary the development of computational methods that shorten the drug discovery pipeline. Toward this end, quantum, and physicochemical molecular descriptors, plus linear discriminant analysis (LDA) were used to analyze the anabolic/androgenic activity of structurally diverse steroids and to discover novel AASs, as well as also to give a structural interpretation of their anabolic-androgenic ratio (AAR). The obtained models are able to correctly classify 91.67% (86.27%) of the AASs in the training (test) sets, respectively. The results of predictions on the 10% full-out cross-validation test al…
Computational discovery of novel trypanosomicidal drug-like chemicals by using bond-based non-stochastic and stochastic quadratic maps and linear dis…
2009
Herein we present results of a quantitative structure-activity relationship (QSAR) studies to classify and design, in a rational way, new antitrypanosomal compounds by using non-stochastic and stochastic bond-based quadratic indices. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop QSAR models based on linear discriminant analysis (LDA). Non-stochastic model correctly classifies more than 93% and 95% of chemicals in both training and external prediction groups, respectively. On the other hand, the stochastic model shows an accuracy of about the 87% for both series. As an experiment of virtual lead generation, the …
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.
Cordycepin analogues of 2',5'-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase.
1991
Analogues of 2',5'-oligoadenylates (2-5A), the cordycepin (3'-deoxyadenosine) core trimer (Co3) and its 5'-monophosphate derivative (pCo3), were shown to display pronounced anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. Treatment of HIV-1 infected H9 cells with 1 microM Co3 or pCo3 resulted in an almost 100% inhibition of virus production. The compounds were encapsulated in liposomes targeted by antibodies specific for the T-cell receptor molecule CD3. Substitution of one or two cordycepin units in Co3 or pCo3 decreased the antiviral activity of the compounds. pCo3 did not stimulate 2-5A-dependent ribonuclease L activity and displayed no effect on the amount of cellular…
Comparative assessment of the toxicology of vitamin A and retinoids in man.
1989
As the title implies, any assessment of the toxic effects of vitamin A derivatives must distinguish between vitamin A in the truest sense, i.e. retinol, and retinoic acid and its synthetic derivatives. Just as no single description is universally applicable to the mode of action of vitamin A derivatives, so too do their toxic effects defy generalization. The recommendation made in 1982 by IUPAC [Eur. J. Biochem., 129 (1989) 1] to designate all derivatives with the typical structure of the vitamin as being retinoids may be chemically logical and correct but, when it comes to describing the effects and side-effects of vitamin A derivatives, it leads to misunderstandings. Retinol, which is fre…
Structure-dynamics-function relationships in Asian elephant (Elephas maximus) myoglobin. An optical spectroscopy and flash photolysis study on functi…
1993
In this work we report the thermal behavior (10–300 K) of the Soret band lineshape of deoxy and carbonmonoxy derivatives of Asian elephant (Elephas maximus) and horse myoglobins together with their carbon monoxide recombination kinetics after flash photolysis; the results are compared to analogous data relative to sperm whale myoglobin. The Soret band profile is modeled as a Voigt function that accounts for the coupling with high and low frequency vibrational modes, while inhomogeneous broadening is taken into account with suitable distributions of purely electronic transition frequencies. This analysis makes it possible to isolate the various contributions to the overall lineshape that; in…
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…
Structural basis for the potential antitumour activity of DNA-interacting benzo[kl]xanthene lignans
2010
The biological properties and possible pharmacological applications of benzo[kl]xanthene lignans, rare among natural products and synthetic compounds, are almost unexplored. In the present contribution, the possible interaction of six synthetic benzo[kl]xanthene lignans and the natural metabolite rufescidride with DNA has been investigated through a combined STD-NMR and molecular docking approach, paralleled by in vitro biological assays on their antiproliferative activity towards two different cancer cell lines: SW 480 and HepG2. Our data suggest that the benzo[kl]xanthene lignans are suitable lead compounds for the design of DNA selective ligands with potential antitumour properties.
Flavonols and flavan-3-ols as modulators of xanthine oxidase and manganese superoxide dismutase activity.
2014
Experiments were performed to assess the dose-dependent effects of quercetin, kaempferol, (+) catechin, and (-) epicatechin on superoxide radical production through the modulation of manganese superoxide dismutase and xanthine oxidase activities. The experiments were carried out at flavanoid concentrations ranging from 1 µM to 100 µM. This investigation highlighted that flavonols induced opposite effects on superoxide radical production at different doses, i.e. pro-oxidant at the highest concentration (100 µM) and anti-oxidant at the lowest concentration (1 µM). Similar behaviors were observed for xanthine oxidase with flavan-3ols. The diastereoisomer (the catechin) acted as a stronger radi…