Articles on the use of Molecular Topology in Drug Discovery & Design
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Topological approach to analgesia
J. Gálvez, R. Garcia-Domenech, J.V. de Julián-Ortiz, R. Soler, Topological approach to analgesia, J. Chem. Inf. Comput. Sci. 34 (1994) 1198-1203.
Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Spain.
In this study we show that by making use of the molecular connectivity indicies, including a new index, which we denominate “δt” and which is obtained from a linear combination of the indicies, as well as from an “
Ε” form index, it is possible to discriminate minor (nonnarcotic) analgesic character with great efficiency, as well as forseeing the analgesic potency of the analyzed compounds, which represents, without a doubt, a powerful tool for the rational design of new analgesic drugs. back to top
Topological approach to drug design
J. Gálvez, R. Garcia-Domenech, J.V. de Julián-Ortiz, R. Soler, Topological approach to drug design, J. Chem. Inf. Comput. Sci. 35 (1995) 272-284.
Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Spain.
In this paper we demonstrated that by an adequate combination of different topological indices it is possible to select and design new active compounds in different therapeutical scopes, with a very high efficiency level. Particularly successful in the search of new "lead drugs", the results show the surprising ability of the topological methods to describe molecular structures. back to top
New cytostatic agents obtained by molecular topology
J. Gálvez, M.J. Gomez-Lechón, R. Garcia-Domenech, J.V. Castell, New cytostatic agents obtained by molecular topology, Bioorganic & Medicinal Chemistry Letters Vol. 6, No. 19 (1996) 2301-2306. back to top
Pharmacological distribution diagrams: A tool for de novo drug design
J. Gálvez, R. Garcia-Domenech, J.V. de Julián-Ortiz, L. Popa, Pharmacological distribution diagrams: a tool for de novo drug design, J. Mol. Graphics 14 (1996) 272-276.
Unidad de Investigacion de Diseno de Farmacos y Conectividad Molecular, Facultad de Farmacia, Universidad de Valencia, Burjassot, Spain. back to top
Discriminant analysis applied to SAR studies using topological descriptors allows us to plot frequency distribution diagrams: a function of the number of drugs within an interval of values of discriminant function vs. these values. We make use of these representations, pharmacological distribution diagrams (PDDs), in structurally heterogeneous groups where generally they adopt skewed Gaussian shapes or present several maxima. The maxima afford intervals of discriminant function in which exists a good expectancy to find new active drugs. A set of beta-blockers with contrasted activity has been selected to test the ability of PDDs as a visualizing technique, for the identification of new beta-blocker active compounds.
Virtual combinatorial syntheses and computational screening of new potential anti-herpes compounds
J.V. de Julián-Ortiz, J. de Gálvez, C. Muñoz-Collado, R. Garcia-Domenech, C. Gimeno-Cardona, Virtual combinatorial syntheses and computational screening of new potential anti-herpes compounds, J. Med. Chem. 42 (1999) 3308-3314.
Unidad de Investigacion de Diseno de Farmacos y Conectividad Molecular, Facultat de Farmacia, and Departamento de Microbiologia, Hospital Clinico Universitario, Universitat de Valencia, Spain. julian@colom.combios.es
The activity of new anti-HSV-1 chemical structures, designed by virtual combinatorial chemical synthesis and selected by a computational screening, is determined by an in vitro assay. A virtual library of phenol esters and anilides was formed from two databases of building blocks: one with carbonyl fragments and the other containing both substituted phenoxy and phenylamino fragments. The library of virtually assembled compounds was computationally screened, and those compounds which were selected by our mathematical model as active ones were finally synthesized and tested. Our antiviral activity model is a "tandem" of four linear functions of topological graph-theoretical descriptors. A given chemical structure was selected as active if it satisfies every discriminant equation in that model. The final result was that five new structures were selected, synthesized, and tested: all of them demonstrated activity, and three showed appreciable anti-HSV-1 activity, with IC(50) values of 0.9 microM. The same model, applied to a database of known compounds, has identified the anti-herpes activity of the following compounds: 3,5-dimethyl-4-nitroisoxazole, nitrofurantoin, 1-(pyrrolidinocarbonylmethyl)piperazine, nebularine, cordycepin, adipic acid, thymidine, alpha-thymidine, inosine, 2, 4-diamino-6-(hydroxymethyl)pteridine, 7-(carboxymethoxy)-4-methylcoumarin, 5-methylcytidine, and others that showed less activity. back to top
Prediction of quinolone activity against mycobacterium avium by molecular topology and virtual computational screening
R. Gozalbes, M. Brun-Pascaud, R. Garcia-Domenech, J. Gálvez, P.M. Girard, J.P. Doucet, F. Derouin, Prediction of quinolone activity against mycobacterium avium by molecular topology and virtual computational screening, Antimicrobial agents and chemotherapy Vol. 44 No. 10 (2000) 2764-2770. back to top
Optimization of a mathematical topological pattern for the prediction of antihistaminic activity
M.J. Duart, R. Garcia-Domenech, G.M. Antón-Fos, J. Gálvez, Optimization of a mathematical topological pattern for the predication of antihistaminic activity, J. Mol. Graphics and Modeling 15 (2001) 561-572. back to top
Predication of the chemiluminescent behavior of pharmaceuticals and pesticides
L. Lahuerta Zamora, Y. Fuster Mestre, M.J. Duart, G.M. Antón Fos, R. Garcia-Domenech, J. Gálvez Álvarez, J. Martínez Calatayud, Prediction of the chemiluminescent behavior of pharmaceuticals and pesticides, Anal. Chem. 73 (2001) 4301-4306. back to top
General topological patterns of known drugs
J. Gálvez, J.V. de Julián-Ortiz, R. Garcia-Domenech, General topological patterns of known drugs, J. Mol. Graphics and Modeling 20 (2001) 84-94. back to top
Search of a topological pattern to evaluate toxicity of heterogeneous compounds
R. Garcia-Domenech, J.V. de Julián-Ortiz, M. J. Duart, J.M. Garcia-Torrecillas, G.M. Anton-Fos, I. Ríos-Santamarina, C. de Gregorio Alapont, J. Gálvez, Search of a topological pattern to evaluate toxicity of heterogeneous compounds, SAR and QSAR in Environmental Research, 2001, Vol. 12, pp. 237-254 back to top
New agents active against Myobacterium avium complex selected by molecular topology: a virtual screening method
Angeles Garcia-Garcia, Jorge Galvez, Jesus-Vicente de Julian-Ortiz, R. Garcia-Domenech, Carlos Munoz, Remedios Guna, and Rafael Borras, New agents active against Myobacterium avium complex selected by molecular topology: a virtual screening method, Journal of Antimicrobal Chemotherapy (2004) 53, 65-73 back to top
New hypoglycaemic agents selected by molecular topology
C. Calabuig, G.M. Anton-Fos, J. Galvez, R. Garcia-Domenach, New hypoglycaemic agents selected by molecular topology, International journal of pharmaceutics 278 (2004) 111-118 back to top
Getting new bronchodilator compounds from molecular topology
Rios-Santamarina Inmaculada, Garcia-Domenech Ramon, Galvez Jorge, Morcillo Esteban Jesus, Santamaria Pedro, Cortijo Julio, Getting new bronchodilator compounds from molecular topology, European journal of pharmaceutical science (2004) 1120 back to top
Prediction of molecular volume and surface of alkanes by molecular topology
Jorge Galvez, rediction of molecular volume and surface of alkanes by molecular topology, J. Chem. Inf. Comput. Sci. back to top
Structural invariants for the prediction of relative toxicities of polychlorodibenzo-p-dioxins and dibenzofurans
J.M. Luco, J. Galvez, R. Garcia-Domenech, and J.V. de Julian-Ortiz, Structural invariants for the prediction of relative toxicities of polyshlorodibenzo-p-dioxins and dibenzofurans, Molecular Diversity, 8: 331-342, 2004. back to top
Computational methods in developing quantitative structure-activity relationships (QSAR): a review.
Dudek AZ, Arodz T, Gálvez J. Comb Chem High Throughput Screen. 2006 Mar;9(3):213-28.
Virtual filtering and screening of combinatorial libraries have recently gained attention as methods complementing the high-throughput screening and combinatorial chemistry. These chemoinformatic techniques rely heavily on quantitative structure-activity relationship (QSAR) analysis, a field with established methodology and successful history. In this review, we discuss the computational methods for building QSAR models. We start with outlining their usefulness in high-throughput screening and identifying the general scheme of a QSAR model. Following, we focus on the methodologies in constructing three main components of QSAR model, namely the methods for describing the molecular structure of compounds, for selection of informative descriptors and for activity prediction. We present both the well-established methods as well as techniques recently introduced into the QSAR domain. back to top
