Corals 7.2 Potential Pharmaceuticals from Soft Corals 191
Part A | 7.2
up-regulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of
the lumbar spinal cord. Additionally, intrathecal injection of lemnalol (10 g) markedly inhibited spinal
pro-inflammatory mediator tumor necrosis factor-˛ expression in microglial cells and astrocytes in neuropathic rats [7.234]. It was recently reported in reference [7.235] that treatment with lemnalol (intramuscular: 30 mg kg
1 , for 6168 h) significantly attenuated
mechanical allodynia, paw edema, and knee swelling
induced by monosodium urate; the elevated expression
of c-Fos and pro-inflammatory proteins observed in
synovial tissue were also significantly inhibited by lemnalol administration rendering the compound a promising candidate for the development of a new treatment
for gouty arthritis and other acute neutrophil-driven inflammatory diseases [7.235].
Genus Scleronephthya
Scleronephthya pallida from Thailand produced a fucoside steroid that exhibited moderate antimalarial activity and cytotoxicity [7.236].
7.2.9 Family Clavulariidae
Genus Clavularia
Kericembrenolides from Clavularia koellikeri were
shown to display growth inhibition against B-16
melanoma cells (IC 50 s of 1:23:8) [7.237]. A cembrane diterpene isolated from the Okinawan C. koellikeri [7.238] showed cytotoxic activity against human colorectal adenocarcinoma cells (DLD-1, IC 50
4:2 g mL
1 ) and strong growth inhibition against human T lymphocytic leukemia cells (MOLT-4, IC 50
0:9 g mL
1 ). C. koellikeri also yielded a new diterpenoid with modest growth-inhibition effect in vitro
toward tumor cells [7.239]. Six cytotoxic dolabellane
diterpenes were isolated from the Formosan soft coral
C. inflata, and their cytotoxicity against selected cancer cells was measured in vitro [7.240]. Three cytotoxic
prostanoids, claviridenone E–G, and three cytotoxic
steroids, stoloniferone E–G, were isolated from the
Formosan C. viridis [7.241]. A cytotoxic cembranoid,
claviolide, was also isolated from the Formosan C. violacea, as reported in reference [7.241]. Clavubicyclone
from C. viridis, a common western Pacific coral, exhibited mild cytotoxicity towards MCF-7 and OVCAR-3
tumor cell lines [7.242]. Extract of C. viridis further
afforded seven new prostanoids [7.243], the pharmacological study of which revealed that bromovulone III
and chlorovulone II exhibited the most promising cytotoxicity (0:5 g mL
1 ) against human prostate (PC-3)
and colon (HT29) cancer cells. Antitumor and anticarcinogenic compounds were isolated from the symbiont
of the Okinawan soft coral C. viridis and showed significant growth-inhibitory activity in vitro toward cancer
cells [7.244].
Corals obviously produce various prostaglandins as
an antipredatory defense [7.245]. Prostaglandins including chlorovolones, clavulones, claviridenones (antitumor prostanoids), and C-20 acetoxy clavulones were
also reported to have been isolated from the stoloniferan
C. viridis, which exhibited unique antineoplastic activity and were potent growth inhibitors in a variety of
cultured cells; thus, they may represent a new chemical class of cancer therapeutics [7.246]. A prostanoid
and steroids of C. viridis were also found to inhibit the
up-regulation of the pro-inflammatory iNOS and COX2 proteins of LPS-stimulated RAW264.7 macrophage
cells [7.227].
Genus Telesto (D Carijoa)
Diverse collections of Carijoa (Telesto) riisei produce a variety of natural products geographically. C.
(Telesto) sp. presented extracts with high cytotoxic activity [7.12]. The Brazilian C. riisei yielded the known
18-acetoxypregna-1,4,20-trien-3-one, which displayed
cytotoxic activity against the cancer cell lines SF295,
MDA-MB435, HCT8, and HL60, as well as antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter spp. and Proteus
spp., all of which are resistant to antibiotics [7.247].
Unusual prostanoids named punaglandins with antiviral and anticancer activities (e.g., an antitumor that
inhibits leukemia cell proliferation) from the octocoral T. (Carijoa) riisei have been reported [7.248].
A steroid (18-acetoxipregna-1,4,20-trien-3-one) isolated from C. riisei displayed a strong antileishmanial
activity, with an IC 50 value of 5:5 g mL
1 against
promastigotes and 16:88 g mL
1 against intracellular
amastigotes [7.249]; the antitrypanosomal activity of
the steroid resulted in an IC 50 value of 50:5 g mL
1 .
The steroid also displayed mammalian cytotoxicity
(IC 50 of 10:6 g mL
1 ). Pregnane compounds from
the Indopacific octocoral Carijoa sp. showed a strong
activity in the preliminary biological assay for the
inhibition of the integrated electron transfer chain
(NADH oxidase activity) in beef heart submitochondrial particles [7.250]. Inhibitory concentration 50%
.IC 50 / ranged from 1:11:9 M, with full inhibition at approximately 21 M. Riiseins A and B from
C. riisei showed in vitro cytotoxicity toward HCT-
Part A | 7.2
up-regulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of
the lumbar spinal cord. Additionally, intrathecal injection of lemnalol (10 g) markedly inhibited spinal
pro-inflammatory mediator tumor necrosis factor-˛ expression in microglial cells and astrocytes in neuropathic rats [7.234]. It was recently reported in reference [7.235] that treatment with lemnalol (intramuscular: 30 mg kg
1 , for 6168 h) significantly attenuated
mechanical allodynia, paw edema, and knee swelling
induced by monosodium urate; the elevated expression
of c-Fos and pro-inflammatory proteins observed in
synovial tissue were also significantly inhibited by lemnalol administration rendering the compound a promising candidate for the development of a new treatment
for gouty arthritis and other acute neutrophil-driven inflammatory diseases [7.235].
Genus Scleronephthya
Scleronephthya pallida from Thailand produced a fucoside steroid that exhibited moderate antimalarial activity and cytotoxicity [7.236].
7.2.9 Family Clavulariidae
Genus Clavularia
Kericembrenolides from Clavularia koellikeri were
shown to display growth inhibition against B-16
melanoma cells (IC 50 s of 1:23:8) [7.237]. A cembrane diterpene isolated from the Okinawan C. koellikeri [7.238] showed cytotoxic activity against human colorectal adenocarcinoma cells (DLD-1, IC 50
4:2 g mL
1 ) and strong growth inhibition against human T lymphocytic leukemia cells (MOLT-4, IC 50
0:9 g mL
1 ). C. koellikeri also yielded a new diterpenoid with modest growth-inhibition effect in vitro
toward tumor cells [7.239]. Six cytotoxic dolabellane
diterpenes were isolated from the Formosan soft coral
C. inflata, and their cytotoxicity against selected cancer cells was measured in vitro [7.240]. Three cytotoxic
prostanoids, claviridenone E–G, and three cytotoxic
steroids, stoloniferone E–G, were isolated from the
Formosan C. viridis [7.241]. A cytotoxic cembranoid,
claviolide, was also isolated from the Formosan C. violacea, as reported in reference [7.241]. Clavubicyclone
from C. viridis, a common western Pacific coral, exhibited mild cytotoxicity towards MCF-7 and OVCAR-3
tumor cell lines [7.242]. Extract of C. viridis further
afforded seven new prostanoids [7.243], the pharmacological study of which revealed that bromovulone III
and chlorovulone II exhibited the most promising cytotoxicity (0:5 g mL
1 ) against human prostate (PC-3)
and colon (HT29) cancer cells. Antitumor and anticarcinogenic compounds were isolated from the symbiont
of the Okinawan soft coral C. viridis and showed significant growth-inhibitory activity in vitro toward cancer
cells [7.244].
Corals obviously produce various prostaglandins as
an antipredatory defense [7.245]. Prostaglandins including chlorovolones, clavulones, claviridenones (antitumor prostanoids), and C-20 acetoxy clavulones were
also reported to have been isolated from the stoloniferan
C. viridis, which exhibited unique antineoplastic activity and were potent growth inhibitors in a variety of
cultured cells; thus, they may represent a new chemical class of cancer therapeutics [7.246]. A prostanoid
and steroids of C. viridis were also found to inhibit the
up-regulation of the pro-inflammatory iNOS and COX2 proteins of LPS-stimulated RAW264.7 macrophage
cells [7.227].
Genus Telesto (D Carijoa)
Diverse collections of Carijoa (Telesto) riisei produce a variety of natural products geographically. C.
(Telesto) sp. presented extracts with high cytotoxic activity [7.12]. The Brazilian C. riisei yielded the known
18-acetoxypregna-1,4,20-trien-3-one, which displayed
cytotoxic activity against the cancer cell lines SF295,
MDA-MB435, HCT8, and HL60, as well as antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter spp. and Proteus
spp., all of which are resistant to antibiotics [7.247].
Unusual prostanoids named punaglandins with antiviral and anticancer activities (e.g., an antitumor that
inhibits leukemia cell proliferation) from the octocoral T. (Carijoa) riisei have been reported [7.248].
A steroid (18-acetoxipregna-1,4,20-trien-3-one) isolated from C. riisei displayed a strong antileishmanial
activity, with an IC 50 value of 5:5 g mL
1 against
promastigotes and 16:88 g mL
1 against intracellular
amastigotes [7.249]; the antitrypanosomal activity of
the steroid resulted in an IC 50 value of 50:5 g mL
1 .
The steroid also displayed mammalian cytotoxicity
(IC 50 of 10:6 g mL
1 ). Pregnane compounds from
the Indopacific octocoral Carijoa sp. showed a strong
activity in the preliminary biological assay for the
inhibition of the integrated electron transfer chain
(NADH oxidase activity) in beef heart submitochondrial particles [7.250]. Inhibitory concentration 50%
.IC 50 / ranged from 1:11:9 M, with full inhibition at approximately 21 M. Riiseins A and B from
C. riisei showed in vitro cytotoxicity toward HCT-