On the Contribution of Molecular Topology to Drug Design and Discovery
The role of molecular topology (MT) in the design and selection of new drugs is discussed. After an overview of the different in silico molecular design current technologies, the QSAR analysis is dealt in detail with particular emphasis in the use of topological indices as molecular descriptors. The results of the application of MT in drug design and discovery are described and finally a possible explanation is given about some of the key reasons explaining its the extraordinary performance.
Keywords: Computer-aided drug design, QSAR, molecular topology, pharmaceutical industry, drug discovery, development, Combinatorial chemistry, high-throughput screening (HTS), lead generation, biological screens, physicochemical, absorption, distribution, metabolism, excretion, toxicological (ADME/Tox) properties, drug-receptor interaction, molecular mechanics, quantum mechanics, Thermodynamic approaches, rational, design methods, rational design, targeted design, drug-receptor design, virtual screening, quantitative structure-activity relationships (QSAR), quantitative structure-property relationships (QSPR), molecular fragments, three-dimensional, molecular parameters, conformers, stereoisomers, enantiomers, pharmacophore, novel drugs discovery, Comparative Molecular Field Analysis (CoMFA), Self Organizing Molecular Field Analysis (SomFA), potent, Modeling tools, regression equations, Mallows parameter, regressions, cross-validation, leave-one-out method, external test set, the linear discriminant analysis, linear combination, Fisher-Snedecor parameter, Mahalanobis distance, discriminant function, multivariate analysis, variance parameter, Wilks' parameter, Classification matrix, Jack-knifed classification matrix, Cross validation with random sub-samples, histogram, in vivo, human cell carcinoma, novel thiopyrano, quinoline, protein kinase C, phosphorylation, polycaspase- dependent apoptosis, chloroquine-sensitive, strains of blood stage, Plasmodium falciparum, concentration, multilinear regression equation, parasitic growth, Mycobacterium avium, microorganism, heterogeneous drugs, microdilution method, connectivity index, Gram-positive bacteria, Staphylococcus aureus, experimental disinfection assay, mycobacteriostatic agents, susceptibility of mycobacteria, Paromomycin, antagonism, structural heterogeneity, non-steroidal anti inflammatories, acute toxicity, pharmacological parameters, lethal dose, multilinear regression, shrinkage estimation, –, ridge regression, Merck Index, Sigma-Aldrich databases, bacterial protein synthesis, spectrum of activity, aerobe, anaerobes, threshold of activity, mordant-Brown, inhibitory concentrations, neohesperidin, silymarine, colorants mordant, computational screening, alkylation, acylation, histamine-induced skin reaction, racemic form, Euclidean distances, topological hybridization
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