INDEX biological action

Chemical Abstracts Service are also producing a similar rapid digest to act as a guide to the literature dealing with the biological action of organic compounds, known as Chemical-Biological Activities. Keyword-in-context, notation, molecular formula and author indexes are provided. 

CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Bruce E. Maryanoff and Cynthia A. Maryanoff. Computer Assisted Molecular Design Related to the Protein Kinase C Receptor, Paul A. Wenderand Cynthia M. Cribbs. Chemistry and Biology of the Immunosuppressant (-)-FK-506, Ichiro Shinkai and Nolan H. Sigal. The Development of Ketorolac Impact on Pyrrole Chemistry and on Pain Therapy, Joseph M. Muchowski. Application of Silicon Chemistry in the Corticosteroid Field, Douglas A. Livingston. Hu-perzine A-A Possible Lead Structure in the Treatment of Alzheimers Disease, Alan P. Kozikowski, X.C, Tang and Israel Hanin. Mechanism-Based-Dual-Action Cephalosporins, Harry A. Albrecht and James G. Christenson. Some Thoughts on Enzyme Inhibitors and the Quiescent Affinity Label Concept, Mien Krantz Index. 

National Center for Toxicological Research (NCTR), FDA. 3900 NCTR Road, Jefferson, AR 72079, U.S.A. URL http //www.fda. gov/nctr/index.html. Mission Statement includes fundamental and applied research specifically designed to define biological mechanisms of action underlying the toxicity of products regulated by the FDA. Covers food safety, bioterrorism, biotechnology, information technology, fundamental and applied research, premarket activities, antimicrobial resistance, and HIV/AIDS. 

From the point of view of synthetic effort, preparation of combinatorial mixtures is by far the most economical approach. It can be done with ordinary laboratory equipment and does not take more time than the synthesis of any one of the individual components of the library. This simplicity, however, has its price firstly, the more components a mixture contains the more difficult it becomes to follow the reaction analytically and to determine the actual composition of the reaction product. Secondly, if hits are found in a biological assay, deconvolution is required. In most cases this is done via resynthesis either of the individual components or of subsets of the mixture. If the composition of the initial mixtures was carefully planned it may be possible to identify the active component(s) by simply comparing the composition of the active mixtures with those of the inactive ones. Corresponding procedures have been reported in the literature (e.g., the techniques of indexed [1,2] and orthogonal [3] chemical libraries have been used in solution-phase synthesis). However, the biological effect of a mixture may also be due to a combined action of several weakly active members, with the result that deconvolution does not identify a significantly active compound. Finally, the problem of impurities multiplies with the complexity of the mixtures. 

This mode of action is not unique since the natural product colchicine, from the autumn crocus Colchicum autumnale (once used as a treatment for gout), also binds to tubulin and disrupts microtubule assembly. It was never seriously considered as an anti-cancer drug owing to its low therapeutic index that is, the dose required to produce clinical benefit was not much greater than the dose causing serious adverse effects or even death. A third plant product with similar biological properties, podophyllotoxin from the American Mayapple, provided the stimulus for research that led to the discovery of another excellent anti-cancer drug - etoposide. 

Biological Should be resistant to enzymatic action May reduce desorptive index, creating a favorable isolated environment... 

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