78
H. Zhu et al.
macrolide moiety and an unsubstituted lactam ring proved to be a prerequisite for
activity against Gram-positive bacteria. The presence of a C-7 hydroxy group, which
has been proposed as a pharmacophore for activity in eukaryotes, does not appear to
be necessary for bacterial transport antagonism.
3.3 Antiparasitic Activities
Actin is also the major protein constituent in cells of parasites, and since actin filaments play a pivotal role in the differentiation and infection processes, the effects
of cytochalasans on parasites have been studied widely. The influence of various
cytochalasans on the growth and differentiation of Entamoeba invadens, a reptile
parasite used as a model system to study such processes in human parasites that cause
amebiasis, was investigated by Makioka and coworkers. At a 10 μM concentration
level, cytochalasins B (110), D (2), E (145) and dihydrocytochalasin B significantly
inhibited the growth of the parasite. Furthermore, at 1 μM, cytochalasin D (2) was
found to inhibit cyst wall formation, which enables parasites at the worm stage to
survive inside or outside (encystation) the host, whereas cytochalasins B (110) and E
(145) and dihydrocytochalasin B were active only at 10 μM. Cytochalasins D (2) and
E (145) also affect excystation [227]. Mori and coworkers screened 431 compounds
and 6,900 samples of microbial broth extracts, and identified aspochalasin B (344),
chaetoglobosin A (210) and prochaetoglobosin III (223) with l-cysteine-dependent
antiamebic activity at 100 μg/cm
3 [228]. Cytochalasin A (110) showed LC 50 values
of 0.0854 ± 0.0019 μg/mm
3 against Aedes aegypti larvae, which is the major vector
of the arboviruses responsible for Dengue fever, one of the most devastating human
infectious diseases [229].
Cytochalasans also showed antiparasitic activities on plant parasites. Meloidogyne
spp., one of the most important groups of plant-parasitic nematodes, has caused
great damage to a wide range of crops worldwide. Hu and coworkers studied the
nematocidal activity of Chaetomium globosum NK102, culture filtrates, and purified chaetoglobosin A (210). The results showed that C. globosum NK102 significantly repelled second-stage juveniles (J2s). Both the culture filtrates and 210 demonstrated strong adverse effects on J2 mortality with 99.8% at 300 μg/cm
3 (LC 50 =
77.0 μg/cm
3 ) at 72 h. Compound 210 and the culture filtrates did not affect egg
hatching until 72 h of exposure. All filtrate treatments inhibited the penetration of
J2 even at a 12.5% dilution treatment. Similarly, 210 (300 and 30 μg/cm
3 ) showed
significant inhibitory effects on J2 penetration. The number of eggs per plant was
significantly reduced using a treatment of 30 mg/kg soil, by 63% relative to control
plants, indicating its apparent negative effect on reproduction of M. incognita. This
study demonstrated the nematocidal activity of 210 and suggested that it could be a
potential biocontrol agent for the integrated management of Meloidogyne incognita
[230]. The nematicidal activity of 210 may be due to its inhibition of the polymerization of monomeric actin (G-actin) to polymeric form (F-actin), and thereby inhibit
cell functions requiring cytoplasmic microfilaments.
H. Zhu et al.
macrolide moiety and an unsubstituted lactam ring proved to be a prerequisite for
activity against Gram-positive bacteria. The presence of a C-7 hydroxy group, which
has been proposed as a pharmacophore for activity in eukaryotes, does not appear to
be necessary for bacterial transport antagonism.
3.3 Antiparasitic Activities
Actin is also the major protein constituent in cells of parasites, and since actin filaments play a pivotal role in the differentiation and infection processes, the effects
of cytochalasans on parasites have been studied widely. The influence of various
cytochalasans on the growth and differentiation of Entamoeba invadens, a reptile
parasite used as a model system to study such processes in human parasites that cause
amebiasis, was investigated by Makioka and coworkers. At a 10 μM concentration
level, cytochalasins B (110), D (2), E (145) and dihydrocytochalasin B significantly
inhibited the growth of the parasite. Furthermore, at 1 μM, cytochalasin D (2) was
found to inhibit cyst wall formation, which enables parasites at the worm stage to
survive inside or outside (encystation) the host, whereas cytochalasins B (110) and E
(145) and dihydrocytochalasin B were active only at 10 μM. Cytochalasins D (2) and
E (145) also affect excystation [227]. Mori and coworkers screened 431 compounds
and 6,900 samples of microbial broth extracts, and identified aspochalasin B (344),
chaetoglobosin A (210) and prochaetoglobosin III (223) with l-cysteine-dependent
antiamebic activity at 100 μg/cm
3 [228]. Cytochalasin A (110) showed LC 50 values
of 0.0854 ± 0.0019 μg/mm
3 against Aedes aegypti larvae, which is the major vector
of the arboviruses responsible for Dengue fever, one of the most devastating human
infectious diseases [229].
Cytochalasans also showed antiparasitic activities on plant parasites. Meloidogyne
spp., one of the most important groups of plant-parasitic nematodes, has caused
great damage to a wide range of crops worldwide. Hu and coworkers studied the
nematocidal activity of Chaetomium globosum NK102, culture filtrates, and purified chaetoglobosin A (210). The results showed that C. globosum NK102 significantly repelled second-stage juveniles (J2s). Both the culture filtrates and 210 demonstrated strong adverse effects on J2 mortality with 99.8% at 300 μg/cm
3 (LC 50 =
77.0 μg/cm
3 ) at 72 h. Compound 210 and the culture filtrates did not affect egg
hatching until 72 h of exposure. All filtrate treatments inhibited the penetration of
J2 even at a 12.5% dilution treatment. Similarly, 210 (300 and 30 μg/cm
3 ) showed
significant inhibitory effects on J2 penetration. The number of eggs per plant was
significantly reduced using a treatment of 30 mg/kg soil, by 63% relative to control
plants, indicating its apparent negative effect on reproduction of M. incognita. This
study demonstrated the nematocidal activity of 210 and suggested that it could be a
potential biocontrol agent for the integrated management of Meloidogyne incognita
[230]. The nematicidal activity of 210 may be due to its inhibition of the polymerization of monomeric actin (G-actin) to polymeric form (F-actin), and thereby inhibit
cell functions requiring cytoplasmic microfilaments.