Marine-Derived Fungal Metabolites 32.3 Marine Organic Compounds 779
Part F | 32.3
Scopararanes C–G (194–198), five new oxygenated
pimarane diterpenes, were isolated from the culture of
a marine sediment-derived fungus Eutypella scoparia
FS26 obtained from the South China Sea [32.139].
All isolated scopararanes (194–198) together with the
known metabolite, libertellenone A (199), were subjected to cytotoxicity (MTT) assay against three human tumor cell lines, namely SF-268 (glioma), MCF7 (breast), and NCI-H460 (NSCLC). Scopararanes C
(194) and D (195) possessed moderate cytotoxic activities against MCF-7 with IC 50 values of 35:9 and
25:6 M, respectively. However, libertellenone A (199)
displayed variable activities with IC 50 values between
12:0 and 40:2 M, whereas the other remaining scopararanes E–G (196–198) displayed weak cytotoxic activities against the MCF-7 cell line with IC 50 values of
more than 70 M [32.139]. Conclusively, the structure–
activity relationship study of compounds 194–199 revealed that the carbonyl group at C-7, the olefinic bond
between C-8 and C-14, and the furan ring formed of
C-20 methyl, C-6, C-5, and C-10, in addition to the
number and positions of hydroxyl groups, could be
important structural features influencing the cytotoxic
activities [32.139].
Geopyxins A–E (200–205), new ent-kaurane diterpenoids, were isolated from endolichenic fungal strains
of the genus Geopyxis [32.140]. The structures and
absolute configurations of geopyxins were established
based on their spectroscopic data and conducting the
modified Mosher’s ester method [32.140]. Methylated
and acetylated derivatives of geopyxins were also prepared and all were assessed for their cytotoxic and
heat-shock induction activities. Results revealed that
geopyxin B (201), and the methylated derivatives of
all geopyxins except geopyxin E (215), exhibited cytotoxic activities in the low micromolar range against
five tumor cell lines, whereas the acetylated derivatives
were found to activate the heat-shock response at similar concentrations [32.140]. Based on these findings, the
preliminary structure-activity motif was deduced to be
the electrophilic ˛; ˇ-unsaturated ketone carbonyl functionality, but this was not sufficient for both cytotoxicity
and heat-shock activation [32.140].
Insuetolides A–C (206–208), three novel meroterpenoids, together with other drimane sesquiterpenes
were isolated from the fungus Aspergillus insuetus (OY207), derived from the Mediterranean sponge Psammocinia sp. [32.141]. Insuetolides featured a hitherto
unprecedented carbon skeleton derived from the cyclization of farnesyl and 3,5-dimethylorsellinic acid. Insuteloide A (206) exhibited weak antifungal activity toward Neurospora crassa with a MIC value of 140 M,
while insuetolide C (208) exhibited mild cytotoxicity
towards MOLT-4 human leukemia cells [32.141].
Three new sesterterpenes, namely ophiobolin K
(209), its 6-epimer (210), and 6-epi-ophiobolin G (211),
were isolated from the marine-derived fungus Emericella variecolor [32.142]. Ophiobolins (209–211) inhibited biofilm formation of Mycobacterium smegmatis
with MICs of 4:165 M; however these compounds
did not show antimicrobial activity at the same concentrations [32.142]. Moreover, ophiobolin K (209)
inhibited also the biofilm formation of M. bovis BCG
and enables restoring the antimicrobial activity of isoniazid against M. smegmatis through inhibiting biofilm
formation [32.142].
In addition to aspergillamides A (44) and B (45,
Fig. 32.6), five new ophiobolin-type sesterterpenoids
(212–216, Fig. 32.11) were isolated from the marinederived fungus Aspergillus ustus derived from the marine sponge Suberites domuncula [32.91]. None of
the isolated sesterterpenoids revealed cytotoxic activity against L5178Y cells at a concentration up to
10 g mL
1 [32.91].
Diaporol A (217), possessing a unique tricyclic
lactone ring, together with eight further new drimane
sesquiterpenoids, diaporols B–I (218–225) were purified from the culture medium of the endophytic fungal
strain Diaporthe sp., derived from the Chinese mangrove Rhizophora stylosa [32.143]. The absolute configurations of compounds 217–221 were established
based on single-crystal X-ray crystallography [32.143].
In the cytotoxicity assay, no compound revealed significant activity against the cell lines tested at concentrations up to 20 M [32.143].
Three new epoxyphomalins C–E (228–230), together with the parent congeners 226 and 227,
were isolated from Paraconiothyrium sp. fermentation extracts [32.144]. The cytotoxic activities of
epoxyphomalins A–E (226–230) were investigated toward a panel of 36 human tumor cell lines. Results
disclosed that 229 possesses selective cytotoxic activities toward PC3M (prostate) and BXF1218L (bladder)
cancer cell lines with IC 50 values of 0:72 and 1:43 M,
respectively [32.144]. Moreover, the inhibitory activity of epoxyphomalin A (226) and B (227) toward
chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes indicated that their cytotoxic
effects are mediated through potent inhibition of the
20S proteasome [32.144].
Three new tetranorlabdane diterpenoids, asperolides A–C (231–233, Fig. 32.12) and five related
Part F | 32.3
Scopararanes C–G (194–198), five new oxygenated
pimarane diterpenes, were isolated from the culture of
a marine sediment-derived fungus Eutypella scoparia
FS26 obtained from the South China Sea [32.139].
All isolated scopararanes (194–198) together with the
known metabolite, libertellenone A (199), were subjected to cytotoxicity (MTT) assay against three human tumor cell lines, namely SF-268 (glioma), MCF7 (breast), and NCI-H460 (NSCLC). Scopararanes C
(194) and D (195) possessed moderate cytotoxic activities against MCF-7 with IC 50 values of 35:9 and
25:6 M, respectively. However, libertellenone A (199)
displayed variable activities with IC 50 values between
12:0 and 40:2 M, whereas the other remaining scopararanes E–G (196–198) displayed weak cytotoxic activities against the MCF-7 cell line with IC 50 values of
more than 70 M [32.139]. Conclusively, the structure–
activity relationship study of compounds 194–199 revealed that the carbonyl group at C-7, the olefinic bond
between C-8 and C-14, and the furan ring formed of
C-20 methyl, C-6, C-5, and C-10, in addition to the
number and positions of hydroxyl groups, could be
important structural features influencing the cytotoxic
activities [32.139].
Geopyxins A–E (200–205), new ent-kaurane diterpenoids, were isolated from endolichenic fungal strains
of the genus Geopyxis [32.140]. The structures and
absolute configurations of geopyxins were established
based on their spectroscopic data and conducting the
modified Mosher’s ester method [32.140]. Methylated
and acetylated derivatives of geopyxins were also prepared and all were assessed for their cytotoxic and
heat-shock induction activities. Results revealed that
geopyxin B (201), and the methylated derivatives of
all geopyxins except geopyxin E (215), exhibited cytotoxic activities in the low micromolar range against
five tumor cell lines, whereas the acetylated derivatives
were found to activate the heat-shock response at similar concentrations [32.140]. Based on these findings, the
preliminary structure-activity motif was deduced to be
the electrophilic ˛; ˇ-unsaturated ketone carbonyl functionality, but this was not sufficient for both cytotoxicity
and heat-shock activation [32.140].
Insuetolides A–C (206–208), three novel meroterpenoids, together with other drimane sesquiterpenes
were isolated from the fungus Aspergillus insuetus (OY207), derived from the Mediterranean sponge Psammocinia sp. [32.141]. Insuetolides featured a hitherto
unprecedented carbon skeleton derived from the cyclization of farnesyl and 3,5-dimethylorsellinic acid. Insuteloide A (206) exhibited weak antifungal activity toward Neurospora crassa with a MIC value of 140 M,
while insuetolide C (208) exhibited mild cytotoxicity
towards MOLT-4 human leukemia cells [32.141].
Three new sesterterpenes, namely ophiobolin K
(209), its 6-epimer (210), and 6-epi-ophiobolin G (211),
were isolated from the marine-derived fungus Emericella variecolor [32.142]. Ophiobolins (209–211) inhibited biofilm formation of Mycobacterium smegmatis
with MICs of 4:165 M; however these compounds
did not show antimicrobial activity at the same concentrations [32.142]. Moreover, ophiobolin K (209)
inhibited also the biofilm formation of M. bovis BCG
and enables restoring the antimicrobial activity of isoniazid against M. smegmatis through inhibiting biofilm
formation [32.142].
In addition to aspergillamides A (44) and B (45,
Fig. 32.6), five new ophiobolin-type sesterterpenoids
(212–216, Fig. 32.11) were isolated from the marinederived fungus Aspergillus ustus derived from the marine sponge Suberites domuncula [32.91]. None of
the isolated sesterterpenoids revealed cytotoxic activity against L5178Y cells at a concentration up to
10 g mL
1 [32.91].
Diaporol A (217), possessing a unique tricyclic
lactone ring, together with eight further new drimane
sesquiterpenoids, diaporols B–I (218–225) were purified from the culture medium of the endophytic fungal
strain Diaporthe sp., derived from the Chinese mangrove Rhizophora stylosa [32.143]. The absolute configurations of compounds 217–221 were established
based on single-crystal X-ray crystallography [32.143].
In the cytotoxicity assay, no compound revealed significant activity against the cell lines tested at concentrations up to 20 M [32.143].
Three new epoxyphomalins C–E (228–230), together with the parent congeners 226 and 227,
were isolated from Paraconiothyrium sp. fermentation extracts [32.144]. The cytotoxic activities of
epoxyphomalins A–E (226–230) were investigated toward a panel of 36 human tumor cell lines. Results
disclosed that 229 possesses selective cytotoxic activities toward PC3M (prostate) and BXF1218L (bladder)
cancer cell lines with IC 50 values of 0:72 and 1:43 M,
respectively [32.144]. Moreover, the inhibitory activity of epoxyphomalin A (226) and B (227) toward
chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes indicated that their cytotoxic
effects are mediated through potent inhibition of the
20S proteasome [32.144].
Three new tetranorlabdane diterpenoids, asperolides A–C (231–233, Fig. 32.12) and five related