Structure-activity relationships biological activities

Structure-Activity Relationships. Biological evaluation of peniciUias yields information such as in vitro and in vivo antibacterial activities. 

Structure—Activity Relationships. Biological evaluation of penicillins yields information such as in vitro and in vivo antibacterial activities, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), protective effectiveness in laboratory animals (PD50), and pharmacokinetic characteristics including efficiency of absorption, serum levels, tissue distribution, urinary excretion, recycling, etc. Penicillins are also tested for ability to resist inactivation by (S-lactamase produced by both gram-positive and gram-negative bacteria,... 

The discovery, synthesis, structure-activity relationships, biology and biochemistry of these compounds are described in this chapter. 

Structure-Activity Relationship Structure-activity relationship (SAR) is the analysis of the quantitative relationship between the biological activity of a set of compounds and their spatial properties using statistical methods. 

This paper reviews the discovery, the structure-activity relationships, insecticidal activity and biological properties of pyridalyl. 

The fundamental assumption of SAR and QSAR (Structure-Activity Relationships and Quantitative Structure-Activity Relationships) is that the activity of a compound is related to its structural and/or physicochemical properties. In a classic article Corwin Hansch formulated Eq. (15) as a linear frcc-cncrgy related model for the biological activity (e.g.. toxicity) of a group of congeneric chemicals [37, in which the inverse of C, the concentration effect of the toxicant, is related to a hy-drophobidty term, FI, an electronic term, a (the Hammett substituent constant). Stcric terms can be added to this equation (typically Taft s steric parameter, E,). 

PW91 (Perdew, Wang 1991) a gradient corrected DFT method QCI (quadratic conhguration interaction) a correlated ah initio method QMC (quantum Monte Carlo) an explicitly correlated ah initio method QM/MM a technique in which orbital-based calculations and molecular mechanics calculations are combined into one calculation QSAR (quantitative structure-activity relationship) a technique for computing chemical properties, particularly as applied to biological activity QSPR (quantitative structure-property relationship) a technique for computing chemical properties... 

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. 

J. P. Hu and co-workers. Structure Activity Relationship oJFlavonoids with Superoxide S cavenging Activity, Biological Trace Element Research, Vol. 47, The Humana Press Inc., Clifton, N.J., pp. 327—331, 1995. 

B-Homosteroids were first reported by Ringold in the course of an investigation of the relationship of structural changes to biological activity of anabolic agents. The Tiffeneau rearrangement sequence described earlier for the preparation of A-homosteroids was used to synthesize 17/ -hydroxy-B-homo-5a-androstan-3-one (56a). 

Structure activity relationships, i.e., the total pattern of change in a biological activity as a function of chemical structure, typically derived from a comparison within a chemical series so that the biological effects of substitution at each structural position may be determined and correlated. 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

Despite the work of Overton and Meyer, it was to be many years before structure-activity relationships were explored further. In 1939 Ferguson [10] postulated that the toxic dose of a chemical is a constant fraction of its aqueous solubility hence toxicity should increase as aqueous solubility decreases. Because aqueous solubility and oil-water partition coefficient are inversely related, it follows that toxicity should increase with partition coefficient. Although this has been found to be true up to a point, it does not continue ad infinitum. Toxicity (and indeed, any biological response) generally increases initially with partition coefficient, but then tends to fall again. This can be explained simply as a reluctance of very hydrophobic chemicals to leave a lipid phase and enter the next aqueous biophase [11]. An example of this is shown by a QSAR that models toxicity of barbiturates to the mouse [12] ... 

The in vivo antihistaminic activity results indicate that all test compounds protected the animals from histamine-induced bronchospasm significantly. Structural activity relationship (SAR) studies indicated that different alkyl substituents on the first position of the triazoloquinazohne ring exerted varied biological activity. 

A httle number of works performing Bfx and Fx quantitative structure-activity relationship (QSAR) studies have been described. On the other hand, to gain insight into the biological behavior of Bfxs and Fxs some studies... 

One of the sources of the fuzziness surrounding these concepts may well be the implicit assumption in structure-activity relationship (SAR) studies that molecular structure contains (i.e. encodes) the information on the biological activity of a given compound. Such an assumption cannot be incorrect, since this would imply the fallacy of SAR studies. However, the assumption becomes misleading if not properly qualified to the effect that the molecular structure of a given compound contains only part of the information on its bioactivity. Indeed, what the structure of a compound encodes is information about the molecular features accounting... 

Testa, B. Drugs as chemical messages molecular structure, biological context, and structure-activity relationships. Med. Chem. Res. 1997, 7, 340-365. 

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