Structure-activity relationships overview

Quantitative Structure—Activity Relationships (QSAR). Quantitative Stmcture—Activity Relationships (QSAR) is the name given to a broad spectmm of modeling methods which attempt to relate the biological activities of molecules to specific stmctural features, and do so in a quantitative manner (see Enzyme INHIBITORS). The method has been extensively appHed. The concepts involved in QSAR studies and a brief overview of the methodology and appHcations are given here. 

Enslein, K. An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol Industrial Health 1988 4 479-98. 

The second modeling approach discussed in this section presents an overview of the fundamentals of quantitative structure-activity relationships (i.e., QSARs [102-130]) and quantitative structure-property relationships (i.e., QSPRs [131-139]). It will show how such an approach can be used in order to estimate and predict sorption/desorption coefficients of various organic pollutants in environmental systems. 

In addition to the synthetic challenge of natural cyclic peptides, these compounds are often isolated in very low yields and thus their structure cannot always be determined without ambiguity. Consequently, total synthesis represents the safest way to prove their constitution, configuration, and even biological activity, since frequently this results from highly active minor contaminants. 10-12 Moreover, synthesis of the natural compounds allows for structural variations as required for structure-activity relationship (SAR) studies to identify the important pharmacophores and their orientation in space. Herein the reader is not provided with a comprehensive overview of the vast list of different natural cyclic peptides, but rather directed to comprehensive reviews. 1,13 Nonetheless, some important and characteristic representative members will be reported in the context of the synthetic methods. 

This chapter provides a brief overview of chemoinformatics and its applications to chemical library design. It is meant to be a quick starter and to serve as an invitation to readers for more in-depth exploration of the field. The topics covered in this chapter are chemical representation, chemical data and data mining, molecular descriptors, chemical space and dimension reduction, quantitative structure-activity relationship, similarity, diversity, and multiobjective optimization. 

Woo, Y.-T. (1983) Carcinogenicity, mutagenicity and teratogenicity of carbamates, fhiocarbamates and related compounds an overview of structure-activity relationships and environmental concerns. Environ. Carcinog. Ecotoxicol. Rev., Cl (1), 97-133. 

Bradbury SP, Russom CL, Ankley GT, Schultz TW, Walker JD. 2003. Overview of data and conceptual approaches for deivation of quantitative structure-activity relationships for ecotoxicological effects of organic chemicals. Environ Toxicol Chem 22 1789-1798. 

Russom CL, Breton RL, Walker JD, Bradbury SP. 2003. An overview of the use of quantitative structure-activity relationships for ranking and prioritizing large chemical inventories for environmental risk assessments. Environ Toxicol Chem 22 ... 

Bradbury, S.P., Quantitative structure-activity-relationships and ecological risk assessment an overview of predictive aquatic toxicology research, Toxicol. Lett., 79, 229-237, 1994. 

A schematic overview of the different structural classes and their TTC values is shown in Eig. 5.7, adapted from data in Cramer et al. (1978) and Kroes et al. (2000, 2004). If the intake of a specific compound is below the TTC value, there should not be a safety concern. In case the intake exceeds the corresponding TTC value, a risk assessment is required on the basis of compound-specific toxicity data. In the latter case, the use of structure-activity relationships (SARs) may be of value. 

Naturally occurring thyrsiferol analogues continue to be an inspiration for many synthetic, biosynthetic, and structure-activity relationship investigations. An overview of the efforts directed toward the biosynthesis of these natural products along with the biological activity displayed by each of the aforementioned compounds is addressed in the next section. 

Through the years a number of different structure-activity relationships (SARs) and receptor models have been developed (for reviews see refs. 91, 92). Therefore this introduction will only give a short overview of the general aspects of dopamine receptor agonist SARs. 

This chapter attempted an overview on the current state of knowledge on structure-activity relationships of this interesting group of plant constituents. Since it is certainly not possible to cover such a wide area exhaustively, and there are probably many studies in the field which were not cited, the author apologizes to all those who might feel their... 

The final chapter, by Itokawa, Takeya, Hitotsuyanagi, and Morita, reviews the various macrocyclic peptide alkaloids isolated from plants. In addition to a general overview of the many new peptide and amide alkaloids that have been isolated recently from a diverse range of plant families, this review places particular emphasis on the structure-activity relationships, the conformational analysis, and the antitumor activity of the RA series of cyclic oligopeptides from Rubia spp. 

See Blagg, J. Structure-activity relationships for In vitro and In vivo toxicity. Annu. Rep. Med. Chem. 2006, 41, 353-368, which also provides a good overview of other types of toxicophores and toxicity considerations. 

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