Bioactive Agents from Natural Sources: Trends in Discovery and Application - Advances in Biochemical Engineering Biotechnology - page 118

sequently, there exists a strong interest in getting access to new therapeutic
agents which is one driving force for advanced drug discovery strategies.New
chemical entities are requested in order to enable therapeutic innovation.An
analogs situation is observable towards new candidates for agricultural appli-
cation.Both,combinatorial chemistry and the exploitation of structural diver-
sity derived from natural sources contribute to improved lead discovery. In
particular, low-molecular mass natural products from bacteria, fungi, plants,
and invertebrates either from terrestric, or marine environments perform
unique structural diversity.In order to get access to this outstanding molecular
diversity various strategies like the (target-directed) biological,physico-chemi-
cal,or chemical screening have been developed.Due to the commercial super-
iority of microbial metabolites this section will focus on chemical diversity
derived from microorganisms.
In the biological screening the selection criterion usually is a wanted biologi-
cal effect aiming at a defined pharmaceutical application (target-directed bio-
logical screening) [137].Biological screening has been developed to a powerful
concept which integrates and makes use ofrecent findings in molecular and cell
biology mounting in high-throughput screening attempts (HTS).Today,success
in drug discovery and development obviously depends on the therapeutic value
of the bioassays running in the primary biological screening,and on the period
required for the identification of first promising lead compounds in order to
start with lead optimization procedures.Therefore,biological screening strate-
gies are considered to be the most profitable ones and are in widespread prac-
tice in pharmaceutical companies.
In contrast to biological screening, the physico-chemical-, and chemical
screening approaches a priori possess no correlation to a defined biological
effect. Here, a selection of promising secondary metabolites out of natural
sources is based on physico-chemical properties,or on the chemical reactivity,
respectively. In both strategies, the first step is chromatography in order to
separate the compounds from the complex mixtures obtained from plants,
microorganisms, fungi, or animals. In a second (analytical) step, physico-
chemical properties or chemical reactivities of the separated secondary meta-
bolites are analyzed.Both strategies have shown to be efficient supplemental and
alternative methods, especially with the aim to discover predominantly new
secondary metabolites.
Chemical screening is based on the analysis of the chemical reactivity of
secondary metabolites using thin-layer chromatography (TLC) [138-146].
Concentrates from natural sources are applied on TLC-plates, chromato-
graphed with different solvent systems (separation step), and their chemical
reactivity is analyzed by making use of defined chemical reagents sprayed
directly onto the TLC plates.Selection criteria are both,the chromatographic
parameters, and the staining (colorization) behavior after spraying and
heating.In a physico-chemical screening selection criteria are the chromato-
graphic behavior (e.g.on C 18 -colums by using HPLC for the chromatographic
step),as well as data from e.g.UV/VIS-,MS-,IR-,or in rare cases NMR spectra.
In most cases, coupling techniques of HPLC with the desired analytical
method are used.