Bioactive Capnosanes and Cembranes from the Soft Coral Klyxum flaccidum

Abstract

Two new capnosane-based diterpenoids, flaccidenol A (1) and 7-epi-pavidolide D (2), two new cembranoids, flaccidodioxide (3) and flaccidodiol (4), and three known compounds 5 to 7 were characterized from the marine soft coral Klyxum flaccidum, collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus Klyxum for the first time. The cytotoxicity of compounds 1 to 7 against the proliferation of a limited panel of cancer cell lines was assayed. The isolated diterpenoids also exhibited anti-inflammatory activity through suppression of superoxide anion generation and elastase release in the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-stimulated human neutrophils. Furthermore, 1 and 7 also exhibited cytotoxicity toward the tested cancer cells, and 7 could effectively inhibit elastase release. It is worth noting that the biological activities of 7 are reported for the first time in this paper.

Metabolites with Anti-Inflammatory Activity from the Mangrove Endophytic Fungus Diaporthe sp. QYM12

“…Macrocyclic sesquiterpenoids and diterpenoids are a functionally diverse group of natural products with versatile bioactivities [ 22 ]. For instance, junceellolide C showed an anti-HBV activity [ 23 ], flaccidenol A displayed a cytotoxic activity [ 24 ], antipacid B exhibited an anti-inflammatory activity [ 25 ], and euphorbesulins A revealed an antimalarial activity [ 26 ]. The anti-inflammatory assay suggested that compound 1 showed a moderate activity with an IC 50 value of 21.5 μM.…”

Cembranoids of Soft Corals: Recent Updates and Their Biological Activities

“…Alzheimer disease [ 82 ] 45 Asperdiol ( 320 ) Known Eunicea knighti Colombian Caribbean Sea Acetylcholinesterase (AChE) inhibition activity with IC 50 value of 0.358 ± 0.130 µM, which showed potential to be develop as neurodegenerative diseases treatment, eg. Alzheimer disease [ 82 ] 46 Flaccidodioxide ( 321 ) New Klyxum flaccidum Along the coast of Pratas Island, Taiwan Low anti-proliferation activity against P388D1 mouse lymphocytic leukemia cell line with IC 50 of 19.6 μg/mL [ 83 ] 47 Flaccidodiol ( 322 ) New Klyxum flaccidum Along the coast of Pratas Island, Taiwan Showed no inhibition activity of superoxide anion and elastase at a concentration of 10 µM relative to the control group [ 83 ] 48 14-O-acetylsarcophytol B ( 323 ) Known Klyxum flaccidum Along the coast of Pratas Island, Taiwan Potent anti-proliferation activity against human lung adenocarcinoma (A549), human colorectal adenocarcinoma (DLD-1), and mouse lymphocytic leukemia (P388D1) cell lines with IC 50 values of 10.8; 11.7; 8.9 μg/ml, respectively. Anti-inflammatory activity by reducing the level of elastase release to 59.66 ± 0.83% with IC 50 value of 7.22 ± 0.85 µM, at a concentration of 10 µM relative to the control group [ 83 ] 49 17- epi -Junceellolide B ( 324 ) New Junceella fragilis Conco Island, Vietnam No significant cytotoxic activity against LNCaP, HepG2, KB, MCF-7, SK-Mel2, HL-60, LU-1 and SW480 cancer cell lines (IC 50 > 100 μM) [ ...…”

“…The later compound was reported to possess no activities. Moreover, a known compound 14-O-acetylsarcophytol B 324 was also reported from the same species [ 83 ]. Junceella fragilis collected from Vietnam was reported to produce new briarane-type diterpenoids, 17- epi -junceellolide B 325 and junceellolide B 326 .…”

“…Tseng et al (2019) isolated 321 and 323 from Taiwanese Klyxum flaccidum which showed anti-cancer activity. 321 displayed low anti-proliferation activity against the P388D1 mouse lymphocytic leukemia cell line with IC 50 of 19.6 μg/mL, while 323 showed a broad range of anti-cancer activities against A549, DLD-1 human colorectal adenocarcinoma, and P388D1 cell lines with IC 50 values of 10.8, 11.7 and 8.9 μg/ml, respectively [ 83 ]. The known compound, 325 , isolated from Vietnamese Junceella fragilis showed weak cytotoxicity against the LNCaP human prostate adenocarcinoma cells with IC 50 of 85.34 μM, as compared with that of the positive control ellipticine (IC 50 of 1.42 μM) [ 84 ].…”

“…A novel cembranoid from Chicoreus ramosus , 302 , showed anti-inflammatory activity through the inhibition of 5-lipooxygenase, with IC 50 of 0.76 mg/mL [ 78 ]. Anti-inflammatory activity was evident in 323 isolated from K. flaccidum, predicted to occur by a reduction in the level of elastase release to 59.66%, with IC 50 of 7.22 µM at a concentration of 10 µM relative to the control group [ 83 ]. Three out of four new cembranoids ( 326, 328, 329 ) isolated from cultured type Briareum violaceum possessed anti-inflammatory activity in LPS-induced RAW 264.7 macrophage cells by significantly inhibiting the expression of iNOS protein to 43, 61, 46%, respectively [ 85 ].…”