Empirical screening

The major dasses of antibiotics are secondary metabolic products of micro-organisms. Many were discovered by empirically screening culture filtrates or cell extracts for antimicrobial activity. A range of techniques (examples are methods using, impregnated discs, porous cylinders, cut wells, see Figure 6.2) have been used to carry out such screening. 

Most of the synthetic applications to date have been based on empirical screening and comparison of ligand systems for effectiveness. A number of useful procedures have been developed. Aryl chlorides are generally less reactive than iodides and... 

A number of approaches have been used to discover new antibiotics in past decades. One approach is empirical screening, in which a whole cell assay is used to find antibacterial activities first, followed by the... 

Empirical drug discovery, despite its successes, is not without intrinsic problems the identification of a lead compound is divorced from an understanding of its mechanism of action, making lead optimization difficult since there is no easily quantifiable way to ascertain whether an analog will have greater effect. Additionally, the value of an empirical screen depends on its predictive ability. In some cases, such as acid hyposecretion or H2-receptor binding assays. 

While cell-based screens have been used in purely empirical screening efforts, they can also be used as the basis of target identification or verification. The... 

As a closing example of the value of asymmetric synthesis in the area of insect chemistry, we describe the synthesis of the stereoisomers of trimedlure, a material discovered by empirical screening and used to monitor for "Medfly" (Figure 9). The commercial preparation of this attractant mixture involves a non-selective addition of HC1 to a substituted cyclohexene. The several products are shown in abbreviated form (Figure 9) the t-butyl esters of this mixture of acids has been employed for many years as a bait for the medfly (19). Each component,... 

Solvent plays a critical role in the development of crystaUization. It can affect strongly the final PSD and crystallization kinetics. However, a solvent is still selected primarily through empirical screening and may be dictated by a previous or subsequent step in the process. Also shown in this example is the impact of supersamration on PSD and form (solvate, oil, and crystalline solid). 

Empirical screening of organic compounds unrelated to existing antibiotics 4... 

Cycloaddition. Through empirical screening the dinuclear Ti complex 4 of 6,6 -diiodo-BINOL and the complex prepared from 5 have been chosen to promote 1,3-dipolar cycloaddition (nitrone -I- enal) and hetero-Diels-Alder reaction (Danishefsky s diene + RCHO), respectively. 

Compounds asterisked have been identihed as present in either the female s abdominal tip or her effluvium. The remaining compounds have been determined as attractants or antagonists of attraction (-) by empirical screening in the field t Flight periods for the lower Hudson Valley of New York according to Chapman and Lienk (1971)... 

At present, the cardinal consideration for the rational design of chemotherapeutic agents is the choice of appropriate biochemical pathways for selective inhibition. Recent developments in the chemotherapy of falciparum malaria exemplify the potential advantages of rational design over empirical screening of compounds. Four years of effort and great expense were required to screen 100,000 compounds for antimalarial activity and the results were essentially negative.The presently preferred... 

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