LC-MS (liquid chromatography–mass detector) and LC-NMR (liquid chromatography–nuclear magnetic resonance spectroscopy).
While in the recent past it was extremely difficult, time consuming and
labour intensive to build such a library from purified natural products, with
the advent of newer and improved technologies related to separation,
isolation and identification of natural products the situation has improved
remarkably. Now, it is possible to build a ‘high quality’ and ‘chemically
diverse’ natural product library that can be suitable for any modern HTS
programmes. Natural product libraries can also be of crude extracts,
chromatographic fractions or semi-purified compounds. However, the best
result can be obtained from a fully identified pure natural product library as
it provides scientists with the opportunity to handle the ‘lead’ rapidly for
further developmental work, e.g. total or partial synthesis, dealing with
formulation factors, in vivo assays and clinical trials.
Source materials
(e.g. plants)
Rapid extraction
e.g. Soxhlet extraction
Extracts
Rapid isolation and purification
e.g. use of HPLC
Isolated compounds
Identification by
spectroscopic techniques,
e.g. UV, IR, MS, NMR
Identified compounds
(Compound library)
HTS
Chemical fingerprinting
or dereplication,
e.g. use of LC-PDA, LC-MS, LC-NMR
Dereplicated extracts
Generation
of 'hit'
Large-scale production
of selected 'hit' compounds
e.g. large-scale isolation
or synthesis
Entry to the further
developmental stages
e.g. preformulation, formulation,
in vivo assays, clinical trials, etc.
To continue to exploit natural sources for drug candidates, the focus must be
on exploiting newer approaches for natural product drug discovery. These
approaches include the application of genomic tools, seeking novel sources
of organisms from the environment, new screening technologies and
improved processes of sample preparation for screening samples. In addition, the recent focus on the synthesis of diversity-oriented combinatorial
libraries based on natural-product-like compounds is an attempt to enhance
the productivity of synthetic chemical libraries.
6.2 Alkaloids
Alkaloids are a naturally occurring large group of pharmacologically active
nitrogen-containing secondary metabolites of plants, microbial or animal
288
CH6 NATURAL PRODUCT CHEMISTRY
While in the recent past it was extremely difficult, time consuming and
labour intensive to build such a library from purified natural products, with
the advent of newer and improved technologies related to separation,
isolation and identification of natural products the situation has improved
remarkably. Now, it is possible to build a ‘high quality’ and ‘chemically
diverse’ natural product library that can be suitable for any modern HTS
programmes. Natural product libraries can also be of crude extracts,
chromatographic fractions or semi-purified compounds. However, the best
result can be obtained from a fully identified pure natural product library as
it provides scientists with the opportunity to handle the ‘lead’ rapidly for
further developmental work, e.g. total or partial synthesis, dealing with
formulation factors, in vivo assays and clinical trials.
Source materials
(e.g. plants)
Rapid extraction
e.g. Soxhlet extraction
Extracts
Rapid isolation and purification
e.g. use of HPLC
Isolated compounds
Identification by
spectroscopic techniques,
e.g. UV, IR, MS, NMR
Identified compounds
(Compound library)
HTS
Chemical fingerprinting
or dereplication,
e.g. use of LC-PDA, LC-MS, LC-NMR
Dereplicated extracts
Generation
of 'hit'
Large-scale production
of selected 'hit' compounds
e.g. large-scale isolation
or synthesis
Entry to the further
developmental stages
e.g. preformulation, formulation,
in vivo assays, clinical trials, etc.
To continue to exploit natural sources for drug candidates, the focus must be
on exploiting newer approaches for natural product drug discovery. These
approaches include the application of genomic tools, seeking novel sources
of organisms from the environment, new screening technologies and
improved processes of sample preparation for screening samples. In addition, the recent focus on the synthesis of diversity-oriented combinatorial
libraries based on natural-product-like compounds is an attempt to enhance
the productivity of synthetic chemical libraries.
6.2 Alkaloids
Alkaloids are a naturally occurring large group of pharmacologically active
nitrogen-containing secondary metabolites of plants, microbial or animal
288
CH6 NATURAL PRODUCT CHEMISTRY