Biomedical Engineering Reference
In-Depth Information
Bioactive Agents from Natural Sources:
Trends in Discovery and Application
Susanne Grabley
1
· Ralf Thiericke
2
Hans-Knöll-Institut für Naturstoff-Forschung e.V.,Beutenbergstrasse 11,D-07745 Jena,Germany
1
E-mail: sgrabley@pmail.hki-jena.de
2
E-mail: thierick@pmail.hki-jena.de
About 30% of the worldwide sales of drugs are based on natural products. Though recom-
binant proteins and peptides account for increasing sales rates,the superiority of low-mole-
cular mass compounds in human diseases therapy remains undisputed mainly due to more
favorable compliance and bioavailability properties.In the past,new therapeutic approaches
often derived from natural products. Numerous examples from medicine impressively
demonstrate the innovative potential of natural compounds and their impact on progress in
drug discovery and development.However,natural products are currently undergoing a phase
of reduced attention in drug discovery because of the enormous effort which is necessary to
isolate the active principles and to elucidate their structures.To meet the demand of several
hundred thousands of test samples that have to be submitted to high-throughput screening
(HTS) new strategies in natural product chemistry are necessary in order to compete success-
fully with combinatorial chemistry.Today,pharmaceutical companies have to spend approxi-
mately US $350 million to develop a new drug.Currently,approaches to improve and accel-
erate the joint drug discovery and development process are expected to arise mainly from
innovation in drug target elucidation and lead finding.Breakthroughs in molecular biology,
cell biology,and genetic engineering in the 1980 s gave access to understanding diseases on
the molecular or on the gene level.Subsequently,constructing novel target directed screening
assay systems of promising therapeutic significance,automation,and miniaturization result-
ed in HTS approaches changing the industrial drug discovery process drastically.Furthermore,
elucidation of the human genome will provide access to a dramatically increased number of
new potential drug targets that have to be evaluated for drug discovery. HTS enables the
testing of an increasing number of samples.Therefore,new concepts to generate large com-
pound collections with improved structural diversity are desirable.
Keywords:
Automation,Biological derivatization,Chemical screening,Combinatorial natu-
ral product chemistry, Drug discovery, High-throughput screening, Natural products,
Physico-chemical screening, Screening bioassays, Structural diversity from nature, Target
identification.
1 Introduction
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
1.1 Natural Products in Drug Discovery and Development . . . . . . . 104
1.2 High-Throughput Screening Towards Lead Discovery . . . . . . . . 105
2 Natural Product-derived Drugs on the Market
. . . . . . . . . . . . 106
2.1 Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
2.2 Immunosuppressant Drugs . . . . . . . . . . . . . . . . . . . . . . 109
2.3 Antihypercholesterolemic Drugs . . . . . . . . . . . . . . . . . . . 111
2.4 Antidiabetic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Search WWH ::
Custom Search