Biological activity of indoles

A growing worldwide problem is drug resistance to disease-inflicting bacteria, such as MRSA (methicillin-resistant Staphylococcus aureus) [45, 46]. Several indoles 

An important strategy for the treatment of cancer is the modulation of microtubule assembly either by preventing its disassembly or by blocking tnbnlin polymerization, and an excellent review is available that discusses several indole leads [98], For example, Silvestri and colleagues report that arylthioindoles are potent inhibitors of tubuhn polymerization [99-101]. For example, 84 inhibits the 

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The indole ring is incorporated into the stmcture of the amino acid tryptophan [6912-86-3] (6) and occurs in proteins and in a wide variety of plant and animal metaboUtes. Much of the interest in the chemistry of indole is the result of efforts to understand the biological activity of indole derivatives in order to develop pharmaceutical appHcations. 

Neuss, N., The spectrum of biological activities of indole alkaloids, in Indole and Biogenetically Related Alkaloids (J. D. Phillipson and M. H. Zenk, eds.), 294-313, Academic Press, London, 1980. 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

An oxime derivative of indirubin (a natural bis-indole alkaloid used in traditional Chinese medicine to treat chronic myelocytic leukemia), indirubin-3 -monoxime (37), was found to be a potent inhibitor of cyclin-dependent kinases (CDKs), and of the proliferation of myeloid leukemia cells via inhibition of a tyrosine kinase . The 3D structure of the complex of 37 with CDK revealed that the oxime function is intact, and that it occupies the ATP-ribose site of the CDK-ATP structure. While the specific role of the oxime group in the biological activity of 37 is not clear, it was proposed that its reactivity may be utilized for further drug design... 

H.-J. Knolker and K. R. Reddy, in "Selected Methods for Synthesis and Modification of Heterocycles The Chemistry and Biological Activity of Natural Indole Systems, Part 1" (V. G. Kartsev, ed.), vol. 4, p. 166. ICSPF Press, Moscow, 2005. 

The biological activity of azoles and their derivatives (indoles, purines, etc.) and their abundance as structural motif in natural products made them a prime target and test ground in the development of catalytic transformations. This chapter is mainly dedicated to the reactions of monocyclic five membered heterocycles and indole. The chemistry of other condensed systems of importance, such as purines, is discussed in Chapter 8. 

BIOLOGICAL ACTIVITY OF PHOSPHORUS-CONTAINING DERIVATIVES OF INDOLE AND PYRROLE... 

Adler and Albert have reported the partition coefficients for the parent azaindoles. The oleyl alcohol-water solubility ratio for the neutral molecules at 25° are 53.2, 36.8,17.3, and 13.1 for 7-, 6-, 5-, and 4-azaindole, respectively. For comparison, indole, which is not basic, is more lipid-soluble, with a ratio of 85.7. The order for the azaindoles does not parallel their basic strength. The per cent of ionization at pH 7. 4 was also calculated and for the above order is 0.15,78.02, 87.87, and 27.75%, respectively. The effects of these properties on the biological activity of the azaindoles is discussed also (see below). 

The synthesis of indoles on soHd supports has been driven by the wide range of indole derivatives that occur in Nature [142-144], and by the biological activity of many indole derivatives of both natural and synthetic origin [145]. The indole scaffold appears in the amino acid tryptophan, the metabolites of which are important in the biochemistry of both plants and animals. In addition, the indole ring appears in many compounds that have found use as drugs, e.g., indomethacin [146], sumatriptan [147], and pindolol [148]. Synthetic approaches towards indoles on solid phases have also been reviewed elsewhere [149]. 

The first detailed investigation of plant growth-regulating activity is linked with the names of Koepfli et al. (1938). On the basis of their experiments with indole and arylalkanoic acids, they established five structural requirements necessary for the biological activity of the molecule. 

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