Biomedical Engineering Reference
In-Depth Information
NH
NH
2
HN
HN
H
NH
OH
OH
OH
Cl
N
H
2
N
Cl
O
O
O
CHO
O
2
N
OH
Streptomycin
H
3
C
OH
O
Chloramphenicol
HO
O
HO
NHCH
3
HO
HO
OH
O
OH
OH
O
O
O
OH
OH
O
O
O
HO
OH
OH
OH
OH
NH
H
3
CO
COOH
H
O
O
O
O
O
OH
O
NH
2
OH
Rifamycin S
Amphotericin B
FIGURE 6.3
Additional examples of antibiotics found during the “Golden Age of antibiotics discovery.”
“Golden Age” of antibiotic discovery, all of the major classes of life-saving antibiotics were found.
The previously illustrated penicillin, vancomycin, tetracycline, and erythromycin represent the
progenitors of the most important classes of antibacterial agents still in use. Other examples of these
wonderfully complex compounds are illustrated in Figure 6.3. Streptomycin, isolated by Waksman
from
Streptomyces griseus
, was the i rst of the class of aminoglycoside antibiotics to be introduced
into therapy. Chloramphenicol, rifamycin, and amphotericin were also discovered during this time
and each has a valuable niche in modern chemotherapy.
In addition to antibiotics used for the treatment of microbial diseases, microbial products have
been explored for a number of other therapeutic uses. Owing to the relative ease with which new
organisms could be isolated from the environment and grown in culture, these provided versatile
sources of new chemistry. Beginning in the 1960s these sources were employed for screening against
other diseases, such as parasitic and fungal infections, as well as for the ability to differentially kill
cancer cells. Notable among the antiparasitic compounds discovered in this way are the milbemy-
cins. These polyketide-derived macrolides, produced by
Streptomyces
species, are exceptionally
effective against several types of parasites that infect livestock. Compounds in the milbemycin class,
e.g., ivermectin and moxidectin (Figure 6.4) have also found utility against the devastating human
disease of river blindness caused by i larial worms, which is endemic to sub-Saharan Africa, and
other tropical areas of the world.
Actinomycete-derived antibiotics with efi cacy as anticancer agents have also been a major focus
of screening programs (see Figure 6.5). Waksman once again discovered the i rst of these, actino-
mycin D, from
Streptomyces parvullus
. Today, actinomycin has quite limited use, but it served as a
prototype for the discovery of other antitumor or antibiotics. Doxorubicin, which interacts similarly
with DNA, was isolated in the 1960s and remains an important component of typical chemotherapy
regimes. Another early discovery from the Golden Age that remains in use today for chemotherapy is
bleomycin. Bleomycin is a complex glycopeptide antibiotic produced by
S. verticillus
that induces
DNA damage through oxidative reactions.
