Bioactive Agents from Natural Sources: Trends in Discovery and Application - Advances in Biochemical Engineering Biotechnology - page 123

Fig. 9. The Natural Product Pool concept to identify new lead structures for drug and agro-
chemical development
grams are directed towards the selection of an optimal candidate for further
drug development.In addition,modification ofa given structure,either synthe-
tic or from nature,may yield new profiles ofbiological activity,eventually giving
access to a new lead compound. Furthermore, testing of compound libraries
consisting of more than 100,000 molecules in the various target-directed bio-
assays designed for hit identification in HTS has shown that numerous mole-
cules interact with more than one target.Therefore,enlarging chemical struc-
ture diversity in order to elaborate test sample libraries of the highest possible
structural diversity is ofsuperior interest for the primary screening run in HTS.
The chemical repertoire for structure generation includes derivatization and
degradation ofa given compound,as well as partial or total synthesis.Today,the
well known “classical” strategies of organic and medicinal chemistry for the
elaboration and variation of chemical structures are supplemented by new
methods and technologies of “combinatorial chemistry”.Combinatorial chem-
istry includes parallel synthesis, as well as split- and split-pool techniques
[196-203]. On solid phase or in solution, combinatorial chemistry strategies
allow efficient and systematic structural variation ofa given chemical structure,
and can advantageously be combined with structural studies on the pharmaco-
logical target. However, strategies of combinatorial chemistry can also be
applied to design compound libraries for HTS aiming at lead discovery.Actual-
ly,combinatorial chemistry,typically in automated procedures,is ofwidespread
use in pharmaceutical and agrochemical research and development. However,
biological methods for structure modification can be a powerful supplementary
tool for derivatization ofstructurally complex molecules from both,natural and
synthetic sources.