Marine-Derived Fungal Metabolites 32.3 Marine Organic Compounds 765
Part F | 32.3
It is nowadays assumed for many secondary
metabolites originally isolated from macroorganisms
that endosymbiotic microorganisms, including fungi
and bacteria, are the real producers. This is highlighted
by the isolation of paclitaxel (Taxol) from an endophytic fungus Taxomyces andreanae obtained from the
inner bark of Taxus brevifolia [32.72], the production
of camptothecin (Campto) by the endophytic fungus
Entrophospora infrequens isolated from Nothapodytes
foetida [32.73], and the production of trabectedin (Yondelis) through a semisynthetic protocol starting with
cyanosafracin B, through fermentation of Pseudomonas
fluroscens on multikilogram scale [32.19]. Therefore,
there has been a sharp increase in research interests with
regard to the exploration of secondary metabolites produced by endosymbiotic microorganisms such as fungi
and bacteria, aiming at establishing a sustainable supply of bioactive natural products that can be further
developed into pharmaceuticals through industrial fermentation or semisynthetic synthesis.
In the next part, we will survey recent reports
on bioactive secondary metabolites from marine-derived fungi from 2010–2012 classified into chemical classes of compounds with particular attention
placed on their structures and reported pharmacological activities.
32.3 Marine Organic Compounds
32.3.1 Alkaloids
Xylarin (1, Fig. 32.5), a [11]cytochalasin derivative,
was purified from the mycelial extract of a marine-derived species of the genus Xylaria isolated from the
gorgonian sea fan Annella sp. collected near the Similan Islands (Thailand) [32.74]. Structurally, xylarin (1)
features a highly substituted perhydroisoindole moiety
to which an octaketide macrocyclic ring derived from
a head-to-tail condensation of eight acetate units affording an unbranched C 16 -polyketide (PKS) moiety is
linked. Antimicrobial activity assay of the crude extract revealed only weak antibacterial activity against
Staphylococcus aureus, whereas the extract was inactive against methicillin-resistant Staphylococcus aureus
(MRSA) [32.74].
Another species of the same fungal genus, obtained
from marine sediment collected in the South China
Sea, produced two new cytochalasins (2 and 3) together with four other known analogs (4–7) [32.75].
All isolated compounds were tested for their in vitro
cytotoxicity against three different human tumor cell
lines MCF-7 (breast), SF-268 (central nervous system,
CNS), and NCI-H460 (lung) using cisplatin as a positive control [32.75]. Among the compounds tested, 21O-deacetylcytochalasin Q (3) was most active against
SF-268 cells (IC 50 D 44:3 M), while cytochalasin D
7) revealed the best activity against MCF-7 cells and
NCI-H460 (IC 50 D 18:6 and 14:4 M, respectively).
Moreover, cytochalasin Q (4) and 19,20-epoxycytochalasin (5) were active against NCI-H460 cells with IC 50
values of 19:7 and 22:6 M, respectively. However,
18-deoxycytochalasin Q (2) and 21-O-deacetyl-19,20epoxycytochalasin Q (6) showed only moderate activity
or were inactive against the cell lines tested [32.75].
Seven new dihydroquinolin-2-one-containing alkaloids, trivially named aflaquinolones A–G (8–14), were
isolated from two different marine fungal isolates of the
genus Aspergillus NRRL58570 and SF-5044 collected
in Hawaii and Korea, respectively [32.76]. In addition,
several known compounds belonging to aspochalasins
and curvularins were also isolated from the Hawaiian
isolate. An absolute configuration of aflaquinolone B
(9) was established based on a nuclear Overhauser and
exchange spectroscopy (NOESY) spectrum, a comparison of calculated and experimental electronic circular
dichroism (ECD) data, and analysis of its Mosher’s
ester derivative [32.76]. All isolated aflaquinolones, except for 11, were subjected to a cytotoxicity assay
against four different human tumor cell lines, however,
no significant activity was reported for the compounds
tested at concentrations up to 80 M [32.76].
From the mycelial extract of the marine-derived
fungus Aspergillus fumigatus, isolated from a Japanese
zoanthid Zoanthus sp., two new indole alkaloids,
2-(3,3-dimethyl-prop-1-ene)-costaclavine (15) and 2(3,3-dimethylprop-1-ene)-epicostaclavine (16), together with the known compounds costaclavine and fumgaclavines A and C, were obtained [32.77]. Relative
and absolute configurations of 15 and 16 were determined based on NOESY,
1 H–
1 H coupling constants,
and CD (circular dichroism) spectra. Compounds 15
and 16 revealed weak cytotoxicity against mouse
leukemia P388 cells [32.77].
Five unusual alkaloids (17–21) were purified from
the culture broth of the endophytic fungus Fusarium
Part F | 32.3
It is nowadays assumed for many secondary
metabolites originally isolated from macroorganisms
that endosymbiotic microorganisms, including fungi
and bacteria, are the real producers. This is highlighted
by the isolation of paclitaxel (Taxol) from an endophytic fungus Taxomyces andreanae obtained from the
inner bark of Taxus brevifolia [32.72], the production
of camptothecin (Campto) by the endophytic fungus
Entrophospora infrequens isolated from Nothapodytes
foetida [32.73], and the production of trabectedin (Yondelis) through a semisynthetic protocol starting with
cyanosafracin B, through fermentation of Pseudomonas
fluroscens on multikilogram scale [32.19]. Therefore,
there has been a sharp increase in research interests with
regard to the exploration of secondary metabolites produced by endosymbiotic microorganisms such as fungi
and bacteria, aiming at establishing a sustainable supply of bioactive natural products that can be further
developed into pharmaceuticals through industrial fermentation or semisynthetic synthesis.
In the next part, we will survey recent reports
on bioactive secondary metabolites from marine-derived fungi from 2010–2012 classified into chemical classes of compounds with particular attention
placed on their structures and reported pharmacological activities.
32.3 Marine Organic Compounds
32.3.1 Alkaloids
Xylarin (1, Fig. 32.5), a [11]cytochalasin derivative,
was purified from the mycelial extract of a marine-derived species of the genus Xylaria isolated from the
gorgonian sea fan Annella sp. collected near the Similan Islands (Thailand) [32.74]. Structurally, xylarin (1)
features a highly substituted perhydroisoindole moiety
to which an octaketide macrocyclic ring derived from
a head-to-tail condensation of eight acetate units affording an unbranched C 16 -polyketide (PKS) moiety is
linked. Antimicrobial activity assay of the crude extract revealed only weak antibacterial activity against
Staphylococcus aureus, whereas the extract was inactive against methicillin-resistant Staphylococcus aureus
(MRSA) [32.74].
Another species of the same fungal genus, obtained
from marine sediment collected in the South China
Sea, produced two new cytochalasins (2 and 3) together with four other known analogs (4–7) [32.75].
All isolated compounds were tested for their in vitro
cytotoxicity against three different human tumor cell
lines MCF-7 (breast), SF-268 (central nervous system,
CNS), and NCI-H460 (lung) using cisplatin as a positive control [32.75]. Among the compounds tested, 21O-deacetylcytochalasin Q (3) was most active against
SF-268 cells (IC 50 D 44:3 M), while cytochalasin D
7) revealed the best activity against MCF-7 cells and
NCI-H460 (IC 50 D 18:6 and 14:4 M, respectively).
Moreover, cytochalasin Q (4) and 19,20-epoxycytochalasin (5) were active against NCI-H460 cells with IC 50
values of 19:7 and 22:6 M, respectively. However,
18-deoxycytochalasin Q (2) and 21-O-deacetyl-19,20epoxycytochalasin Q (6) showed only moderate activity
or were inactive against the cell lines tested [32.75].
Seven new dihydroquinolin-2-one-containing alkaloids, trivially named aflaquinolones A–G (8–14), were
isolated from two different marine fungal isolates of the
genus Aspergillus NRRL58570 and SF-5044 collected
in Hawaii and Korea, respectively [32.76]. In addition,
several known compounds belonging to aspochalasins
and curvularins were also isolated from the Hawaiian
isolate. An absolute configuration of aflaquinolone B
(9) was established based on a nuclear Overhauser and
exchange spectroscopy (NOESY) spectrum, a comparison of calculated and experimental electronic circular
dichroism (ECD) data, and analysis of its Mosher’s
ester derivative [32.76]. All isolated aflaquinolones, except for 11, were subjected to a cytotoxicity assay
against four different human tumor cell lines, however,
no significant activity was reported for the compounds
tested at concentrations up to 80 M [32.76].
From the mycelial extract of the marine-derived
fungus Aspergillus fumigatus, isolated from a Japanese
zoanthid Zoanthus sp., two new indole alkaloids,
2-(3,3-dimethyl-prop-1-ene)-costaclavine (15) and 2(3,3-dimethylprop-1-ene)-epicostaclavine (16), together with the known compounds costaclavine and fumgaclavines A and C, were obtained [32.77]. Relative
and absolute configurations of 15 and 16 were determined based on NOESY,
1 H–
1 H coupling constants,
and CD (circular dichroism) spectra. Compounds 15
and 16 revealed weak cytotoxicity against mouse
leukemia P388 cells [32.77].
Five unusual alkaloids (17–21) were purified from
the culture broth of the endophytic fungus Fusarium