Chemistry Reference
In-Depth Information
12.12 ANTIPARASITIC AGENTS
Avermectins (
114
,
115
) are a series of macrocyclic lactones that are
broad-spectrum, highly potent, glutamate-gated, chloride channel-modulator
antiparasitic agents produced by
Streptomyces avermitilis
(146, 147). Ivermectin,
23,24-dihydroavermectin B
1
a
/B
1
b
(
116
), was the first product approved in
the mid-1980s for treatment of intestinal parasites in domesticated and farm
animals, and it remains the standard of care (148, 149). The remarkable activity
of ivermectin against
Onchocerca volvulus
, the causative parasitic agent of
onchocerciasis (river blindness), led to clinical development and the approval of
Mectizan
®
Merck & Co., Inc., Whitehouse Station, NJ; for the treatment of such
diseases. These parasitic diseases have debilitated millions of people in many
countries in Africa and South America. Because Mectizan
®
is a very effective
treatment, Merck is providing this drug free of cost to all people in need as a
part of the “Mectizan Donation Program,” which has had tremendous impact on
the health and quality of life of people affected by these diseases (150).
Spinosyns were discovered from the fermentation broth of
Saccharopolyspora
spinosa
by screening for mortality of blowfly larvae, and a mixture of spinosyns
A(
117
)andD(
118
) was approved and used successfully as a crop protection
and an antiparasitic animal health agent. (151) Nodulisporic acids are an indole
diterpenoid class discovered from various species of
Nodulisporium
as orally
active antiflea and antitick agents for dogs and cats (152, 153). The most active
OCH
3
HO
OCH
3
CH
3
O
O
24
23
O
O
O
CH
3
O
R
O
O
OH
O
H
OH
23,24
(
114
)
Avemectin B
1a
, R
=
CH(CH
3
)CH
2
CH
3
,
Δ
23,24
(
115
)
Ivermectin R
=
CH(CH
3
)CH
2
CH
3
+
CH(CH
3
)
2
, (
116
)
Avermecin B
1b
, R
=
CH(CH
3
)
2
,
Δ
(H
3
C)
2
N
O
OMe
O
OMe
OMe
H
O
H
O
H
O
O
O
N
OH
H
3
CH
2
C
O
H
H
H
OH
H
H
OH
O
R
Spinosyn A, R
=
H (
117
)
Nodulisporic Acid A (
119
)
Spinosyn D, R
=
Me (
118
)
