Biomedical Engineering Reference
In-Depth Information
Closely related to alkaloids are the peptides, that are composed largely of amino acids, often
with unusual structural modii cations. These peptides are characteristically much smaller than
proteins, generally less than 2000 Da in molecular weight, and are usually not assembled on the
ribosome. As shown in Figure 6.1, the powerful antibiotics, penicillin and vancomycin, are repre-
sentatives of nonribosomally synthesized peptide natural products that have great utility in modern
medicine.
Terpenoids comprise a highly diverse class of secondary metabolites, whose members are
constituted by combinations of i ve-carbon units. These segments are commonly referred to as
“isoprenoid units” that are biogenetically derived from one of two alternative pathways, either
through mevalonic acid or deoxyxylulose phosphate. Traditionally, these compounds have been
characterized as monoterpenes (C10), e.g., menthol and camphor; sesiquiterpenes (C15), e.g.,
artemisinin; diterpenes (C20), e.g., paclitaxel (Taxol
®
); and so on to sesterterpenes (C25), and
triterpenes (C30). The obvious structural diversity is derived from cation-induced rearrangements
of the nascent isoprenyl chain to form a large variety of cyclic frameworks.
Polyketides are the result of an exceptionally versatile biosynthetic pathway that assembles
polyfunctional compounds by sequential condensation of small carboxylic acid units, followed by
various steps, such as reductive processing, “tailoring” reactions, and cyclization. The range of
structural diversity of polyketides is so vast that it is difi cult to summarize with only a few exam-
ples, so for illustration two of the best known antibiotic polyketides, tetracycline and erythromycin
are shown in Figure 6.1.
These biosynthetic origins remain basically the same across the phylogenetic spectrum; however,
the distribution of various pathways is highly dependent on the type of organism. Polyketides and
nonribosomally synthesized peptides, particularly those with antimicrobial activity have been
primarily isolated from bacteria and fungi. Higher plants are historically the most prolii c sources
of terpenes and alkaloids. Since higher plants are readily accessible they were the i rst sources to be
explored for medicinal properties.
6.2 HISTORICALPERSPECTIVE
Plants have been used as medicines for centuries, according to folklore, often without any perceptible
efi cacy. Plant materials were processed for medicinal use by chopping and grinding into powders
or through aqueous extraction to make teas, smoking, or chewing. Often mixtures of plant products
were combined ostensibly to create the most benei cial medicines. While the majority of these
products were not effective, it was an accepted practice, and other than faith healing there was no
real alternative.
Despite the difi culties encountered by administering mixtures of plant products in these crude
preparations, several have yielded medicinally useful products upon purii cation. Opium, a dried
concentrate of the milky latex derived from the poppy,
P. somniferum
, has been used for thousands
of years as an analgesic. Recreational smoking of opium for its euphoric effect became popular in
Europe in the early nineteenth century. Morphine (see Figure 6.1), which is the major active alkaloid
in opium, is a powerful pain medicine, but owing to its addictive properties, it is mainly prescribed
for the management of pain in terminal illnesses.
Malaria is an infectious disease caused by protozoan parasites of the genus
Plasmodium
.
Symptoms of malaria have been treated with a number of plant preparations. Cinchona bark was
originally discovered to have antimalarial properties in South America in the early 1600s and was
soon imported to Europe where it was widely prescribed. Chemical investigations in the early
1800s by Pelletier and others led to the isolation of purii ed alkaloids possessing the antima-
larial properties of the plant materials. Quinine (Figure 6.1), the major active principle obtained in
this work, soon became the preferred treatment for symptoms of malaria and was manufactured
through large-scale isolation from the bark. The advent of substituting purii ed chemicals for crude
