Marine-Derived Fungal Metabolites 32.3 Marine Organic Compounds 777
Part F | 32.3
the EtOAc extract of the endophytic fungus Corynespora cassiicola, isolated from the inner leaf tissues of
the Chinese mangrove medicinal plant Laguncularia
racemosa [32.132]. Absolute configurations of 170–
172 were established by TDDFT ECD calculations of
their solution conformers, proving that they belong to
the (11S) series of xestodecalactones, opposite to the
(11R) configurations of the known xestodecalactones
A–C [32.132]. Compounds 170–174 were subjected to
antibacterial, antiproliferative, antifungal, and antitrypanosomal activities. None of them proved to be active
in any of these cellular screens. However, in a biochemical protein kinase activity assay using 16 different
human protein kinases, only corynesidone B and 6-(3
0 -
hydroxybutyl)-7-O-methylspinochrome B (174) exhibited significant activities against several kinases with
IC 50 values in the low micromolar range [32.132].
32.3.4 Terpenes
Aspergiterpenoid A (175), ()-sydonol (176), ()sydonic acid (177), and ()-5-(hydroxymethyl)-2(2
0 ,
6
0 ,6
0 -trimethyltetrahydro-2H-pyran-2-yl)phenol (178),
four new bisabolane-type sesquiterpenoids, were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp. derived from the sponge
Xestospongia testudinaria [32.133]. All isolated compounds revealed selective antibacterial activity toward
eight bacterial strains with MIC values between 1:25
and 20:0 M [32.133]. In the antifouling assay, only
178 inhibited larval settlement of the barnacle Balamus
amphitrite at 100 M concentration [32.133].
Another isolate of the fungus Aspergillus sp. was
obtained from the same marine sponge X. testudinaria collected in the South China Sea and afforded
three new phenolic bisabolane sesquiterpenoid dimers,
namely disydonols A–C (179–181) [32.134]. The isolated compounds were evaluated for their cytotoxic
activity against HepG-2 and Caski human tumor cell
lines using MTT assay. Results revealed that only
disydonol A (179) and C (181) exhibited potent cytotoxic activities toward these two cell lines with IC 50
values between 6:0 and 26:0 M, while disydonol B
(180) was found to be relatively noncytotoxic (IC 50 >
200 M) [32.134].
In addition to prenylated indole alkaloids,
carneamides A–C (61–63, Fig. 32.6) and quinazoline derivatives, carnequinazolines A–C (64–66), a new
drimane sesquiterpenoid, 9˛-hydroxy-5˛-drim-7-ene6-one-11,12-olide (182, Fig. 32.10), was isolated from
the fungus Aspergillus carneus derived from the brown
alga Laminaria sachalinensis [32.99]. Structurally, 182
was identified as a drimane sesquiterpenoid featuring
a -lactone ring and enone group in its molecule and
biologically it revealed no significant activity in either
cytotoxic or antimicrobial assays [32.99].
Asperaculin A (183), an unprecedented sesquiterpenoid featuring a novel [5,5,5,6]fenestrane ring system, was isolated from the fungus Aspergillus aculeatus
CRI323-04 isolated from the marine sponge Xestospongia testudinaria [32.135]. Asperaculin A (183) did
not exhibit cytotoxic activity (at 50 g mL
1 ) against
HepG2, MOLT-3, A549, and HuCCA-1 cancer cell
lines [32.135].
In addition to the alkaloid fumiquinazoline K
(40, Fig. 32.6), a new nordammarane triterpenoid,
6ˇ, 16ˇ-diacetoxy-25-hydroxy-3,7-dioxo-29-nordammara-1,17(20)-dien-21,24-lactone (184, Fig. 32.10),
was isolated from the marine fungus Aspergillus fumigatus KMM-4631 associated with the soft coral
Sinularia sp. [32.89]. Compound 184 did not exhibit
activity in either cytotoxic or antimicrobial activity
assays [32.89].
A novel antioxidant agent, JBIR-124 (185), was
purified from the marine sponge-derived fungus Penicillium citrinum [32.136]. Structurally, 185 is identical
to the known antioxidant agent JBIR-59 (186) and
it differs only in the presence of additional methyl
group at C-2. In the radical scavenging (2,2-Diphenyl1-picryl-hydrazyl, DPPH) assay, JBIR-124 (185) and
JBIR-59 (186) exhibited potent antioxidant activities
with IC 50 values of 30 and 25 M, respectively, compared to ˛-tocopherol as a positive control (IC 50 D
9 M) [32.136].
Penicisteroids A (187, Fig. 32.11) and B (188), two
polyoxygenated steroids, were reported as new metabolites from the endophytic fungus Penicillium chrysogenum QEN-24S isolated from an unidentified species
of the red algal genus Laurencia [32.137]. Penicisteroid A (187) featured tetrahydroxy and C-16-acetoxy
functionalities and exhibited potent antifungal and selective cytotoxic activities compared to penicisteroid
B (188) and anicequol (189) [32.137]. These differences in bioactivity illustrated that the hydroxyl group
at C-6 in the B ring is likely to be an important structural feature for the antifungal activity, whereas the
moderate activity of 187 and 189 illustrated that one
or more substitutions of hydroxyl group at the B ring
could contribute to the antifungal activity. Moreover,
the hydroxyl group at C-6 in the B ring proved to be
essential for the cytotoxicity as in penicisteroid A (187)
compared to 188 and 189 [32.137].
Part F | 32.3
the EtOAc extract of the endophytic fungus Corynespora cassiicola, isolated from the inner leaf tissues of
the Chinese mangrove medicinal plant Laguncularia
racemosa [32.132]. Absolute configurations of 170–
172 were established by TDDFT ECD calculations of
their solution conformers, proving that they belong to
the (11S) series of xestodecalactones, opposite to the
(11R) configurations of the known xestodecalactones
A–C [32.132]. Compounds 170–174 were subjected to
antibacterial, antiproliferative, antifungal, and antitrypanosomal activities. None of them proved to be active
in any of these cellular screens. However, in a biochemical protein kinase activity assay using 16 different
human protein kinases, only corynesidone B and 6-(3
0 -
hydroxybutyl)-7-O-methylspinochrome B (174) exhibited significant activities against several kinases with
IC 50 values in the low micromolar range [32.132].
32.3.4 Terpenes
Aspergiterpenoid A (175), ()-sydonol (176), ()sydonic acid (177), and ()-5-(hydroxymethyl)-2(2
0 ,
6
0 ,6
0 -trimethyltetrahydro-2H-pyran-2-yl)phenol (178),
four new bisabolane-type sesquiterpenoids, were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp. derived from the sponge
Xestospongia testudinaria [32.133]. All isolated compounds revealed selective antibacterial activity toward
eight bacterial strains with MIC values between 1:25
and 20:0 M [32.133]. In the antifouling assay, only
178 inhibited larval settlement of the barnacle Balamus
amphitrite at 100 M concentration [32.133].
Another isolate of the fungus Aspergillus sp. was
obtained from the same marine sponge X. testudinaria collected in the South China Sea and afforded
three new phenolic bisabolane sesquiterpenoid dimers,
namely disydonols A–C (179–181) [32.134]. The isolated compounds were evaluated for their cytotoxic
activity against HepG-2 and Caski human tumor cell
lines using MTT assay. Results revealed that only
disydonol A (179) and C (181) exhibited potent cytotoxic activities toward these two cell lines with IC 50
values between 6:0 and 26:0 M, while disydonol B
(180) was found to be relatively noncytotoxic (IC 50 >
200 M) [32.134].
In addition to prenylated indole alkaloids,
carneamides A–C (61–63, Fig. 32.6) and quinazoline derivatives, carnequinazolines A–C (64–66), a new
drimane sesquiterpenoid, 9˛-hydroxy-5˛-drim-7-ene6-one-11,12-olide (182, Fig. 32.10), was isolated from
the fungus Aspergillus carneus derived from the brown
alga Laminaria sachalinensis [32.99]. Structurally, 182
was identified as a drimane sesquiterpenoid featuring
a -lactone ring and enone group in its molecule and
biologically it revealed no significant activity in either
cytotoxic or antimicrobial assays [32.99].
Asperaculin A (183), an unprecedented sesquiterpenoid featuring a novel [5,5,5,6]fenestrane ring system, was isolated from the fungus Aspergillus aculeatus
CRI323-04 isolated from the marine sponge Xestospongia testudinaria [32.135]. Asperaculin A (183) did
not exhibit cytotoxic activity (at 50 g mL
1 ) against
HepG2, MOLT-3, A549, and HuCCA-1 cancer cell
lines [32.135].
In addition to the alkaloid fumiquinazoline K
(40, Fig. 32.6), a new nordammarane triterpenoid,
6ˇ, 16ˇ-diacetoxy-25-hydroxy-3,7-dioxo-29-nordammara-1,17(20)-dien-21,24-lactone (184, Fig. 32.10),
was isolated from the marine fungus Aspergillus fumigatus KMM-4631 associated with the soft coral
Sinularia sp. [32.89]. Compound 184 did not exhibit
activity in either cytotoxic or antimicrobial activity
assays [32.89].
A novel antioxidant agent, JBIR-124 (185), was
purified from the marine sponge-derived fungus Penicillium citrinum [32.136]. Structurally, 185 is identical
to the known antioxidant agent JBIR-59 (186) and
it differs only in the presence of additional methyl
group at C-2. In the radical scavenging (2,2-Diphenyl1-picryl-hydrazyl, DPPH) assay, JBIR-124 (185) and
JBIR-59 (186) exhibited potent antioxidant activities
with IC 50 values of 30 and 25 M, respectively, compared to ˛-tocopherol as a positive control (IC 50 D
9 M) [32.136].
Penicisteroids A (187, Fig. 32.11) and B (188), two
polyoxygenated steroids, were reported as new metabolites from the endophytic fungus Penicillium chrysogenum QEN-24S isolated from an unidentified species
of the red algal genus Laurencia [32.137]. Penicisteroid A (187) featured tetrahydroxy and C-16-acetoxy
functionalities and exhibited potent antifungal and selective cytotoxic activities compared to penicisteroid
B (188) and anicequol (189) [32.137]. These differences in bioactivity illustrated that the hydroxyl group
at C-6 in the B ring is likely to be an important structural feature for the antifungal activity, whereas the
moderate activity of 187 and 189 illustrated that one
or more substitutions of hydroxyl group at the B ring
could contribute to the antifungal activity. Moreover,
the hydroxyl group at C-6 in the B ring proved to be
essential for the cytotoxicity as in penicisteroid A (187)
compared to 188 and 189 [32.137].