Quantitative structure-bioactivity relationships QSAR

Certain computational methodologies such as some approaches to quantitative structure-activity relationship (QSAR) studies use 3D ligand structures [37, 38]. These methods generally assume that a bioactive conformation has been estab-Hshed for a set of molecules and that these conformers can be ahgned in a maimer that reflects the relative orientation they would adopt in a binding site. It is thus... 

Cuba, W. and Cruciani, G. Molecular field-derived descriptors for the multivariate modelling of pharmacokinetic data, in Mdecular Modelling and Prediction of Bioactivity, Proceedings of the 12th European Symposium on Quantitative Structure-Activity Relationships (QSAR 98), Gundertofte, K. and Jorgensen, F.S. (Eds). Plenum Press, New York, 2000, 89-95. 

The underlying theory of Quantitative Structure-Activity Relationship (QSAR) is that biological activity is directly related to molecular structure. Therefore, molecules with similar structure will possess similar bioactivities for similar proteins/receptors/enzymes and the changes in structure will be represented through the changes in the bioactivities. The best general description of a QSAR model is... 

Correlating analog structure with bioactivity via quantitative structure-activity relationship (QSAR) studies... 

The correlation of bioactivity data with Eq. 1 or some relationship derived from it results, if successful, in a correlation equation called a quantitative structure activity relationship (QSAR). 

These efforts were guided by the study of quantitative structure-activity relationships (QSAR) following the Hansch approach. In this method linear free-energy related and other electronic, hydrophobic, and steric substituent constants are used for a quantitative analysis of the possible ways in which substituents may modulate bioactivity in a congeneric series. In the QSAR studies of benzoylphenyl ureas the electronic Hammett a-constants and the hydro-phobic Hansch n-constants were used. To measure the steric influences, steric substituent constants of a new type (B1,B2,B3,B4, and L) were applied which had recently been introduced by us and which give improved correlations in comparison with the steric Es constants used in the literature hitherto (21, 22). The constants B- toBj are measures of the widths of substituents in four rectangular directions. The L-constant accounts for the length of a substituent ... 

Cruciani G, Crivori P, Carrupt PA, Testa B (2000) Molecular fields in quantitative structure-permeation relationships The VolSurf approach. Theochem 503 17-30 Cruciani G, Pastor M, Clementi S (2000) Handling information from 3D GRID maps for QSAR studies. In Gun-dertofte K, Jorgensen FS (eds) Molecular modelling and prediction of bioactivity, proceedings of the 12th European symposium on quantitative structure-activity relationships (QSAR 98). Plenum Press, New York, pp 73-81 Cruciani G, Pastor M, Guba W (2000) VolSurf A new tool for the pharmacokinetic optimization of lead compounds. Eur J Pharm Sd 11 S29-S39... 

Zhang et al. [36] combine DFT-based conformation analysis with quantitative structure-activity relationship (QSAR) analysis. They looked at bioactive conformations for 25 cyclic imide derivatives as proto-porphyrinogen oxidase (PPO) inhibitors. PPO is the last common enzyme in the biosynthetic... 

For years, we have been studying QSAR (quantitative structure-activity relationship) analyses of pesticides and other bioactive compounds. In many examples, we have found a decisive role of the steric effect in determining the activity variation. In this chapter, applications of various steric constants such as E E°, Vw and STERIMOL parameters to QSAR studies mostly from our own laboratory are reviewed. 

Lajiness MS (1991) Evaluation of the performance of dissimilarity selection methodology. In Silipo C, Vittoria A (eds) QSAR rational approaches to the design of bioactive compounds. Proceedings of the VIII European symposium on quantitative structure-activity relationships. Sorrento, Italy, 9-13 Sept 1990. ESCOM, Leiden, pp 201-204... 

J. K. Seydel, QSAR and Strategies in the Design of Bioactive Compounds. Proceedings of the 5th European Symposium on Quantitative Structure-Activity Relationships, Bad Segeberg, Federal Republic of Germany, 17-21 September 1984, VCH, Weinheim,... 

A. Miklavc and D. Hadzi, in QSAR, Rational Approaches to the Design of Bioactive Compounds Proceedings of the Eighth European Symposium on Quantitative Structure-Activity Relationships, C Silipo and A. ttoria, Ms., Elsevier Science Publishers, Amsterdam, 1991, pp. 71-00. Delineating the Role of Hydrophobicity in Quantitative Structure-Activity Relationships. 

In order to provide a model data base for testing quantitative structure activity relationships, the unique wealth of the numerous and diverse biological data dispersed in the literature is hsted in about 110 tables, put in relation to each other and other standard compounds, together with many structural formulas of the compounds involved. A number of data are published for the first time. Some of the more important recent QSAR-studies are briefly acknowledged. Conformational aspects of bioactive pyrethroids are discussed (from synthesis, QSAR, X-ray) some of the X-ray derived conformations are pubhshed for the first time. 

Since his undergraduate years, his research career has focused on the structure-activity relationships of bioactive compounds, starting with the auxin-type plant-growth regulators and herbicides. In 1961, he joined Corwin Hansch at Pomona College in Claremont, California, as a Postdoctoral Research Fellow. From 1961 to 1963, he and Hansch developed a novel procedure to quantitatively analyze structure-activity relationships of agrochemicals and medicines (QSAR). QSAR is regarded as a forerunner to the development of a number of recent computer-aided... 

Abstract A thorough antimicrobial review of an increasing number of reports reveals a broad spectrum of research activity in the development practices that are used to treat a variety of diseases. The quantitative relationship between chemical structure and biological activity has received considerable attention in recent years because it allows one to predict theoretically bioactivity without an inordinate amount of experimental time and effort. In this chapter we collect and discuss critically published results concerning the QSAR research on antimicrobial compounds. Finally, we present an updated perspective about the future trends in this area. 

The quantitative relationship between chemical structure and biological activity allows one to predict theoretically bioactivity without resorting to an inordinate amount of time and effort making the experimental determinations. Many attempts have been performed to elucidate the QSAR of antimicrobials by using different physicochemical parameters. 

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