Biomedical Engineering Reference
In-Depth Information
1
Introduction
1.1
Natural Products in Drug Discovery and Development
Although interest in natural products as a source of innovation in drug disco-
very has decreased in the last few decades, therapeutics of microbial or plant
origin count for more than 30% of the current worldwide human therapeutics
sales.Considering the top-twenty drugs of1997 approximately 40% derive from
nature, and in the time period from 1992 to 1996 34% of the new chemical
entities (NCE) introduced were natural compounds. For anticancer and anti-
infective treatment even 60% of the approved drugs and the pre-new drug
application candidates (excluding biologics) are of natural origin for the period
1989 to 1995 [1]. These figures demonstrate the evidence of natural product
research,and its impact on drug discovery and development.Furthermore,data
reflecting recent trends emphasize the superior role ofnatural products as both,
valuable lead compounds and potential new drugs [2].
In the future,novel chemical structures with improved therapeutic properties
by affecting new disease targets can be expected to arise from genomic sciences.
Structural and functional analysis of the human genome gives access to an
increasing number of disease related genes and their products,thus,hopefully
contributing to more causal therapies [3].In order to drive foreward the drug
discovery and development process an active principle substantially affecting a
disease target is requested. In most cases, first hits are discovered by random
screening approaches. Subsequent validation steps follow to answer the key
question whether a hit will give rise to a lead compound that will prove bene-
ficial for optimizing structure/activity relationship by the well established
powerful tools of rational drug design.Issues of interest not only comprise bio-
activity at the target ofinterest but also applicability,bioavailability,biostability,
metabolism,toxicity,specificity ofbioactivity,distribution,tissue selectivity,cell
penetration properties,and as a key prerequisite for development,access to large
quantities ofthe compound for clinical studies and commercialization has to be
guaranteed [4].
In the past,compounds from nature often opened up completely new thera-
peutic approaches. Moreover, natural compounds substantially contributed to
identify and understand novel biochemical pathways in vitro and in vivo,and
consequently proved to make available not only valuable drugs but also essen-
tial tools in biochemistry,and molecular cell biology.It is worth while studying
exhaustively the molecular basis of biological phenomena of new and/or un-
usual chemical structures from nature. Numerous examples from medicine
impressively demonstrate the innovative potential ofnatural products and their
impact on progress in drug discovery and development as discussed below.
Further examples can be added from agricultural use:
i) The herbicide phosphinothricin (glufosinate, Basta) represents a unique
methyl phosphinic acid analog of glutamic acid acting as a strong competi-
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