Bioactive diversity

Dixon, J.S. and Villar, H.O. (1998). Bioactive Diversity and Screening Library Selection via Affinity Fingerprinting. J.Chem.Inf.Comput.ScL, 38,11%-1203. 

Chemical Diversity The unrelatedness of a set of, for example, building blocks or members of a combinatorial library, as measured by their properties such as atom connectivity, physical properties, computational measurements, or bioactivity. Diverse chemical libraries are widely and evenly dispersed in the multidimensional property space. Chemical diversity has two major elements, redundancy and coverage. 

More recently, Che et al. reported a tandem asymmetric reaction of ami-nobenzaldehydes (or aminophenones) with allqmes to give chiral bioactive diversely substituted tetrahydroquinolines. The first step catalysed by a... 

Over the last few years the number of heterocyclic N—F reagents has developed tremendously (Fig. 1). The driving force for this interest has been the need for easily accessible and safe reagents capable of the selective fluorination of bioactive molecules. Generated by reaction of F2 with the parent compound, products are obtained that are capable of fluorinat-ing species as diverse as carbanions and aromatics depending on their fluorinating power. 

The formation of triiodothyronine (T3) and tetra-iodothyronine (thyroxine T4) (see Figure 42—2) illustrates many of the principles of diversity discussed in this chapter. These hormones require a rare element (iodine) for bioactivity they are synthesized as part of a very large precursor molecule (thyroglobuhn) they are stored in an intracellular reservoir (colloid) and there is peripheral conversion of T4 to T3, which is a much more active hormone. 

The biological activity of a compound can often be affected dramatically by the presence of even a single fluorine substituent that is placed in a particular position within the molecule. There are diverse reasons for this, which have been discussed briefly in the preface and introduction of this book. A few illustrative examples of bioactive compounds containing a single fluorine substituent are given in Fig. 3.1. These include what is probably the first example of enhanced bioactivity due to fluorine substitution, that of the corticosteroid 3-1 below wherein Fried discovered, in 1954, that the enhanced acidity of the fluorohydrin enhanced the activity of the compound.1 Also pictured are the antibacterial (3-fluoro amino acid, FA (3-2), which acts as a suicide substrate enzyme inactivator, and the well-known anti-anthrax drug, CIPRO (3-3). 

Hamann, M.T. (2003) Enhancing marine natural product structural diversity and bioactivity through semisynthesis and biocatalysis. Current Pharmaceutical Design, 9, (11) 879-889. 

Phytochemicals or phytonutrients are bioactive substances that can be found in foods derived from plants and are not essential for life the human body is not able to produce them. Recently, some of their characteristics, mainly their antioxidant capacity, have given rise to research related to their protective properties on health and the mechanisms of action involved. Flavonoids are a diverse group of phenolic phytochemicals (Fig. 6.1) that are natural pigments. One function of flavonoids is to protect plants from oxidative stress, such as ultraviolet rays, environmental pollution, and chemical substances. Other relevant biological roles of these pigments are discussed in other chapters of this book. 

Finally, it should also be considered that flavonoid-rich foods contain a great diversity of compounds with bioactive properties (for e.g., carotenoids, other phenolics, fiber, and minerals), and multiple interactions occur among all of them. There is also great diversity in the ingestion, absorption, and metabolism of these compounds in different populations, and all of these circumstances could camouflage any effect of flavonoids on disease prevention or treatment. 

Seidah, N. G. and Chretien, M. Proprotein and prohormone convertases a family of subtilases generating diverse bioactive polypeptides. Brain Res. 848 45-62,1999. 

---