Chemistry Reference
In-Depth Information
H
2
N
NH
HO
NO
2
NH
OH
HO
O
OH
CHO
O
NH
2
HN
NMe
2
HO
H
H
OH
HN
O
OH
Cl
2
HCOCHN
NH
2
OH
NH
2
OH
OH
OH
O
O
OH
OH
OH
O
O
HO
Streptomycin (
21
)
Chloramphenicol (
22
)
Tetracycline (
23
)
Cl
NMe
2
HO
OH
NMe
2
H
H
H
H
OH
OH
NH
2
NH
2
OH
OH
O
OH
OH
O
OH
O
O
OH
O
O
Doxycycline (
25
)
Chlortetracycline (
24
)
NMe
2
NMe
2
NMe
2
NMe
2
H
H
H
H
OH
OH
O
H
N
NH
2
NH
2
H
OH
OH
O
OH
OH
O
OH
O
O
OH
O
O
Minocycline (
26
)
Tigecycline (
27
)
agents such as the aza derivatives, azithromycin (
29
) and ketolide (telithromycin,
30
) (13, 14). Mupirocin (pseudomonic acid,
31
) is another protein synthesis
inhibitor that was isolated from
Pseudomonas fluorescens
and is used only as a
topical agent (6).
Vancomycin (
32
), a glycopeptide produced by
Streptomyces orientalis
,isa
key Gram-positive antibiotic, originally discovered in 1954, and remains a crit-
ical antibiotic in clinical practice even today for the treatment of Gram-positive
bacterial infections (6). Teicoplanin (
33
), a related glycopeptide produced by
Streptomyces teicomyceticus
, is a newer antibiotic that complements vancomycin
in the clinic but is not effective against vancomycin-resistant bacteria. Ramo-
planin (
34
) represents another glycopeptide that is larger in molecular size and
structurally different from vancomycin and teicoplanin; it is in the late stages
of clinical development for treatment of Gram-positive bacterial infections. Gly-
copeptides inhibit the bacterial cell wall. Daptomycin (
35
), a cyclic lipopeptide
produced by
Streptomyces roseosporus
, is one of the newest members of antibi-
otics approved for the clinical practice as a broad-spectrum Gram-positive agent.
It works by depolariztion of the bacterial cell membrane (14). Streptogramins
were discovered in the early 1960s but were used for humans only recently when
a 70/30 mixture of dalfopristin (
36
) and quinupristin (
37
) with the trade name
Synercid
®
King Pharmaceuticals, Bristol, NJ; was developed for the treatment
of drug-resistant Gram-positive bacterial infections (15).
