Marine-Derived Fungal Metabolites 32.3 Marine Organic Compounds 767
Part F | 32.3
rived fungus and its host. The isolated stachylines were
subjected to a large number of bioactivity assays including cytotoxicity, antidiabetic, antimicrobial, NF-ÄB
inhibitory activity assay, and protein kinase inhibition
assays, but no activity was recognized in any of these
assays [32.79].
Penipanoid A (24), an unprecedented triazole carboxylic acid derivative, together with two quinazolines alkaloids, penipanoids B (25) and C (26), and
a quinazoline derivative (27) were isolated from the
marine sediment-derived fungus Penicillium paneum
SD-44 [32.80]. The structure of 24 was confirmed
by X-ray crystallography establishing the compound
as the first triazole metabolite from marine sedimentderived fungi, whereas 25 featured an unusual quinazolinone structure possessing a dihydroimidazole ring
system [32.80]. In the antiproliferative activity assay,
penipanoid A (24) revealed activity against the SMMC7721 cell line (IC 50 D 54:2 M), while penipanoid D
(27) exhibited significant activity against A-549 and
BEL-7402 cell lines with IC 50 values of 17:5 and
19:8 M, respectively, compared to fluorouracil which
displayed IC 50 values of 13:0, 13:7, and 21:8 M
against the above three cell lines [32.80].
Aspergicin (28) was reported as a new alkaloid together with the previously known neoaspergillic acid
from mixed culture mycelia of two epiphytic fungi from
the genus Aspergillus isolated from a rotten fruit of the
marine mangrove plant Avicennia marina [32.81]. Both
aspergicin and neoaspergillic acid revealed significant
antimicrobial activity against some Gram-positive and
Gram-negative bacteria with minimum inhibitory concentrations (MICs) between 2:2 and 43:0 M [32.81].
Acremolin (29), an unprecedented modified base
featuring a 1H-azirine moiety, was purified from the
culture broth of the marine-derived fungus Acremonium
strictum, isolated from an unidentified Korean Choristida sponge [32.82]. Structurally, acremolin (29) is
a modified guanine base attached to an isoprene unit
via a 1H-azirine moiety. In the cytotoxicity assay, acremolin (29) revealed only weak activity against A549
cells with IC 50 of 200 M [32.82].
Together with stachylines (23 and 24), and marilines A–C (30–32), phthalimide derivatives reported as
novel metabolites were obtained from the same extract
of the marine-derived fungus Stachylidium sp. [32.83].
The absolute configurations of the enantiomeric congeners marilines A 1 (30a) and A 2 (30 b / were established by a combination of experimental circular
dichroism (CD) investigations and quantum chemical
CD calculations. Marilines A 1 (30a) and A 2 (30 b / inhibited the serine protease human leukocyte elastase
(HLE) with an IC 50 value of 0:86 M for both enantiomers [32.83]. HLE is an enzyme considered to be
a main cause of tissue damage accompanying inflammatory diseases such as chronic obstructive pulmonary
disease, cystic fibrosis, and adult respiratory distress
syndrome [32.84, 85]. Therefore, inhibitory activity exhibited by marilines A 1 (30a) and A 2 (30 b / against
HLE potentiates the tendency to use them as therapeutically useful candidates for the treatment of those
diseases. Mariline B (31) did not exhibit inhibitory
activity against HLE. Marilines A 1 (30a), A 2 (30 b /,
and B (31) showed antiplasmodial activity against the
liver stages of Plasmodium berghei with IC 50 values
of 6:7, 11:6, and 13:8 M, respectively [32.83]. Mariline A 1 (30a) and A 2 (30 b / were assessed for their
cytotoxic activity against panels of 5 and 19 cancer
cell lines with mean GI 50 values of 24:4 and 11:0 M,
respectively [32.83].
Unusual polyketide-type alkaloids, (-)-cereolactam
(33, Fig. 32.6) and (-)-cereoaldomine (34) comprising
a lactam ring and an iminine functionality, respectively,
were produced together with the related metabolite
(-)-trypethelone by the marine endophytic fungus Coniothyrium cereale obtained from the green alga Enteromorpha sp. [32.86]. Both 33 and 34 selectively
inhibited the activity of HLE with IC 50 values of 9:3
and 3:0 M, respectively [32.86].
Auranomides A–C (35–37) are three new alkaloids
that have been reported from the marine-derived fungus Penicillium aurantiogriseum [32.87]. Structurally,
auranomides A (35) and B (36) featured a new scaffold containing a quinazoline-4-one substituted with
a pyrrolidin-2-iminium moiety. In the cytotoxicity assay against human tumor cell lines, auronamide B (36)
was the most potent compound with an IC 50 value of
97 M [32.87].
Two new epimeric alkaloids, namely tumonoic
acids K (38) and L (39), were isolated together with
several known compounds from the marine-derived
fungus Penicillium citrinum [32.88]. Compounds 38
and 39 represent the first example of tumonoic acid
analogs derived from a fungus [32.88]. Tumonoic acids
K and L revealed weak cytotoxic activity against A375 cell lines with IC 50 values of 65:7 and 124:6 M,
respectively [32.88].
Fumiquinazoline K (40), a quinazoline-type alkaloid, was isolated from a marine strain of Aspergillus
fumigatus KMM 4631 associated with the soft coral
Part F | 32.3
rived fungus and its host. The isolated stachylines were
subjected to a large number of bioactivity assays including cytotoxicity, antidiabetic, antimicrobial, NF-ÄB
inhibitory activity assay, and protein kinase inhibition
assays, but no activity was recognized in any of these
assays [32.79].
Penipanoid A (24), an unprecedented triazole carboxylic acid derivative, together with two quinazolines alkaloids, penipanoids B (25) and C (26), and
a quinazoline derivative (27) were isolated from the
marine sediment-derived fungus Penicillium paneum
SD-44 [32.80]. The structure of 24 was confirmed
by X-ray crystallography establishing the compound
as the first triazole metabolite from marine sedimentderived fungi, whereas 25 featured an unusual quinazolinone structure possessing a dihydroimidazole ring
system [32.80]. In the antiproliferative activity assay,
penipanoid A (24) revealed activity against the SMMC7721 cell line (IC 50 D 54:2 M), while penipanoid D
(27) exhibited significant activity against A-549 and
BEL-7402 cell lines with IC 50 values of 17:5 and
19:8 M, respectively, compared to fluorouracil which
displayed IC 50 values of 13:0, 13:7, and 21:8 M
against the above three cell lines [32.80].
Aspergicin (28) was reported as a new alkaloid together with the previously known neoaspergillic acid
from mixed culture mycelia of two epiphytic fungi from
the genus Aspergillus isolated from a rotten fruit of the
marine mangrove plant Avicennia marina [32.81]. Both
aspergicin and neoaspergillic acid revealed significant
antimicrobial activity against some Gram-positive and
Gram-negative bacteria with minimum inhibitory concentrations (MICs) between 2:2 and 43:0 M [32.81].
Acremolin (29), an unprecedented modified base
featuring a 1H-azirine moiety, was purified from the
culture broth of the marine-derived fungus Acremonium
strictum, isolated from an unidentified Korean Choristida sponge [32.82]. Structurally, acremolin (29) is
a modified guanine base attached to an isoprene unit
via a 1H-azirine moiety. In the cytotoxicity assay, acremolin (29) revealed only weak activity against A549
cells with IC 50 of 200 M [32.82].
Together with stachylines (23 and 24), and marilines A–C (30–32), phthalimide derivatives reported as
novel metabolites were obtained from the same extract
of the marine-derived fungus Stachylidium sp. [32.83].
The absolute configurations of the enantiomeric congeners marilines A 1 (30a) and A 2 (30 b / were established by a combination of experimental circular
dichroism (CD) investigations and quantum chemical
CD calculations. Marilines A 1 (30a) and A 2 (30 b / inhibited the serine protease human leukocyte elastase
(HLE) with an IC 50 value of 0:86 M for both enantiomers [32.83]. HLE is an enzyme considered to be
a main cause of tissue damage accompanying inflammatory diseases such as chronic obstructive pulmonary
disease, cystic fibrosis, and adult respiratory distress
syndrome [32.84, 85]. Therefore, inhibitory activity exhibited by marilines A 1 (30a) and A 2 (30 b / against
HLE potentiates the tendency to use them as therapeutically useful candidates for the treatment of those
diseases. Mariline B (31) did not exhibit inhibitory
activity against HLE. Marilines A 1 (30a), A 2 (30 b /,
and B (31) showed antiplasmodial activity against the
liver stages of Plasmodium berghei with IC 50 values
of 6:7, 11:6, and 13:8 M, respectively [32.83]. Mariline A 1 (30a) and A 2 (30 b / were assessed for their
cytotoxic activity against panels of 5 and 19 cancer
cell lines with mean GI 50 values of 24:4 and 11:0 M,
respectively [32.83].
Unusual polyketide-type alkaloids, (-)-cereolactam
(33, Fig. 32.6) and (-)-cereoaldomine (34) comprising
a lactam ring and an iminine functionality, respectively,
were produced together with the related metabolite
(-)-trypethelone by the marine endophytic fungus Coniothyrium cereale obtained from the green alga Enteromorpha sp. [32.86]. Both 33 and 34 selectively
inhibited the activity of HLE with IC 50 values of 9:3
and 3:0 M, respectively [32.86].
Auranomides A–C (35–37) are three new alkaloids
that have been reported from the marine-derived fungus Penicillium aurantiogriseum [32.87]. Structurally,
auranomides A (35) and B (36) featured a new scaffold containing a quinazoline-4-one substituted with
a pyrrolidin-2-iminium moiety. In the cytotoxicity assay against human tumor cell lines, auronamide B (36)
was the most potent compound with an IC 50 value of
97 M [32.87].
Two new epimeric alkaloids, namely tumonoic
acids K (38) and L (39), were isolated together with
several known compounds from the marine-derived
fungus Penicillium citrinum [32.88]. Compounds 38
and 39 represent the first example of tumonoic acid
analogs derived from a fungus [32.88]. Tumonoic acids
K and L revealed weak cytotoxic activity against A375 cell lines with IC 50 values of 65:7 and 124:6 M,
respectively [32.88].
Fumiquinazoline K (40), a quinazoline-type alkaloid, was isolated from a marine strain of Aspergillus
fumigatus KMM 4631 associated with the soft coral