Quantitative SAR studies

Posner and coworkers have developed versatile methodology for the synthesis of novel 1,2,4-trioxanes that has allowed detailed investigation of their Structure-Activity Relationships (SAR) , while Jefford and coworkers first synthesized fenozan BO-7, so naturally some of their work has centered on its mechanism of action. Avery and coworkers have also contributed significantly to the area by the syntheses and QSAR (Quantitative SAR) studies of many artemisinin analogues. 

One goal of SAR studies is to put forward a pharmacophore model that can elucidate the activities of synthesized derivatives, as well as predict the activity of novel derivatives. A three-dimensional quantitative SAR study was attempted for ginkgolides and the PAF receptor, using comparative molecular field analysis and 25 ginkgolide analogs, mainly those synthesized by Corey et al. " In agreement with the SAR studies just described, this pharmacophore model predicted that substituents in the lO-OH position of GB would improve activity. 

Masson F and Rabalais J W 1991 Time-of-flight scattering and recoiling spectrometry (TOF-SARS) analysis of Pt 110. I. Quantitative structure study of the clean (1 x 2) surface Surf. Sc/. 253 245-57... 

First, the qualitative and quantitative variability of the amount of catechins and proanthocyanidins present in plant extracts used for different studies is probably the most significant. This might be due to the use of different procedures of extraction, quantification and structural elucidation. In most cases, even the lack of rigorous phytochemical characterization and quantification of active compoimd(s) constitutes a severe limitation on the rehabihty of the results. The lack of commercially available pure standards (particularly for some proanthocyanidins) represents an additional problem that has so far hampered the execution of rigorous SAR studies. This hmitation means that although a munber of in vitro or in vivo studies have been carried out by using more or less pure standards of catechins or with plant extracts containing both catechins and proanthocyanidins, only a handful of authors have... 

QSAR means quantitative SAR. It is a model that relates the chemical structure to an activity. In the so-called SAR the quantitative aspect of the phenomenon is not addressed, and the study refers to categories, such as toxic and non toxic. In a certain way, this is a simplified version of the QSAR model. The expression QSAR sometimes covers both cases. If the modeled feature is a property, the expression QSPR is also used. 

Structure-activity relationship (SAR) studies including qualitative and quantitative SAR. 

Significant efforts have been made to assemble teratogenic data basses with peer-reviewed evaluations (ref. 1). New avenues for the SAR studies have been opened, such as quantitative methods for structural superposition of molecules and for superposition of their reactivity characteristics (ref. 2). Emphasis has been placed on the electrostatic properties of the molecules, such as the molecular electrostatic potential, the electric fields, and the polarizability terms calculated from perturbation expansions (ref. 2). Computer-assisted multivariate SAR which deals with many variables simultaneously has been advanced (ref. 3). 

Even though much is already known about the toxicity of diterpene alkaloids that contribute to the toxicity of Consolida, Delphinium, and Aconitium species, no antiviral study has been so far reported on this type of alkaloids. Therefore, no SAR studies have been encountered by us on the antiviral or antimicrobial activities of these alkaloids. However, a quantitative SAR analysis performed on a number of diterpene alkaloids isolated from an Aconitum sp. indicated that biological activity of these alkaloids may be related to their toxicity rather than to a specific pharmacological action [40]. In a current study on 43 norditerpenoid alkaloids from Consolida, Delphinium, and Aconitum species against several tumor cell lines, lycoctonine and browniine were... 

The qualitative analysis of SARs described above has shed light on the highly complex nature of SARs. In medicinal chemistry, SARs are typically analyzed on a case-by-case basis. Thus far, few if any approaches have been introduced to systematically and quantitatively describe SAR characteristics of different compound classes. In the following, two related approaches are presented that provide a quantitative measure of SAR characteristics only based on 2D structural similarity and binding data. Limiting similarity assessment to 2D molecular representations departs from the 3D similarity-oriented correlation studies described above, but makes it possible to extend quantitative SAR analysis to targets for which no, or only few, relevant X-ray structures are available. 

The relationship between a chemical s structure and its biological action has been studied extensively for over a century (16). In cases where there is not a complete understanding of the mechanism/mode of action or where the influence of functional groups is not known or obvious, there is a vast body of knowledge on how different structural features within a class of chemicals may correlate with various levels of hazard. Structure-activity relations (SAR) or their mathematical treatment. Quantitative SAR (QSAR) have been developed for myriad endpoints including cancer, developmental and reproductive effects, aquatic toxicity, boiling points, water solubility and many others hazard endpoints. An instructor therefore has many opportunities to incorporate the concept of SAR at several points in the curriculum. 

Structure-activity relationship (SAR) studies are based on the assumption that similar molecules elicit similar activities in a lock/key-type manner. Quantitative structure-activity relationships (QSARs) correlate the extent of a change in a biological response (e.g., activity) elicited by a specific compound with its physicochemical and/or its structural properties,... 

It is important to understand different approaches to the representation of the effects of changes in chemical structures. The free-energy parameters can be estimated from values determined by physical-chemical studies of model compounds and analogs. Such parameters are continuous variables, and may assume any reasonable value. Without them, quantitation of SAR would result only in additivity effects of the type determined in the so-called yes or no indicator to SAR 13). However, even the use of the simple yes or no indicator variables in SAR studies can result in useful coefficients which indicate the relative importance of these terms. These coefficients are determined by regression analysis. 

The researchers started analysis of SAR studies in the late 19th century. The concept of quantitatively correlating physicochemical properties of molecules with their biological activities, known as, quantitative structure-... 

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