Natural products pharmacokinetic properties

The extraordinary biological activity of epothilones has spurred interest of scientists around the world. Indeed, several epothilones and many derivatives are currently in different phases of clinical trials for the treatment of various forms of cancer. Also the synthetic community has given a great deal of attention to these remarkable compounds, probably more than to any other compound in the last ten years. This is not very surprising, because in comparison to paclitaxel (which until recently was one of the main success stories of natural products research), the epothilones have a relatively simple structure, which allows easier modification, and they display higher in vitro activity as well as better pharmacokinetic properties. 

Gottlieb NL. Comparative pharmacokinetics of parenteral and oral gold compounds. J Rheumatol 1982 9 (SuppI 8) 99-109. Blocka K. Auranofin versus injectable gold Comparison of pharmacokinetic properties. Am J Med 1983 75(6A) 114-122. Abraham EP, Chain E, Baker W, Robinson R. Penicillamine, a characteristic degradiation product of penicillin. Nature 1943 151 107. 

Wermuth, C. G. Modulation of natural substances in order to improve their pharmacokinetic properties. In Natural Products as Medicinal Agents (Beal, J. L., Reinhard, E., Eds). Hippokrates Verlag Stuttgart, 1981, pp. 185-216. 

In the case of natural products with the major purpose of chemical defense, it can be expected that they have been optimized in the course of evolution not only with respect to pharmacodynamic but also to such pharmacokinetic aspects, i.e. many if not all compounds of such a group should show physicochemical properties leading to good bioavailability. 

Natural products derived from 1,2,3-triazole are not known. The 1,2,3-triazole structure is contained in a number of pharmaceuticals (see p 473). It is used, for example, to modify the pharmacokinetic properties of the clinically employed y -lactam antibiotic cefatrizin 14 ... 

Natural products are amenable to further improvement, whether in terms of efficacy and selectivity for the biological target or the achievement of optimal pharmacokinetic properties... 

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