Bioactivities of six sterols isolated from marine invertebrates.
BACKGROUND
Epidioxy sterols and sterols with special side chains, such as hydroperoxyl sterols, usually obtained from marine natural products, are attractive for bioactivities.


OBJECTIVE
To isolate and screen bioactive and special sterols from China Sea invertebrates.


METHODS
Two hydroperoxyl sterols (1 and 2) from the sponge Xestospongia testudinaria Lamarck (Petrosiidae), three epidioxy sterols (3-5) from the sea urchin Glyptocidaris crenularis A. Agassiz (Glyptocidaridae), sponge Mycale sp. (Mycalidae) and gorgonian Dichotella gemmacea Milne Edwards and Haime (Ellisellidae) and an unusual sterol with 25-acetoxy-19-oate (6) also from D. gemmacea were obtained and identified. Using high-throughput screening, their bioactivities were tested toward Forkhead box O 3a (Foxo3a), 3-hydroxy-3-methylglutaryl CoA reductase gene fluorescent protein (HMGCR-GFP), nuclear factor kappa B (NF-κB) luciferase, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), protein-tyrosine phosphatase 1B (PTP1B), mitochondrial membrane permeabilization (MMP) and adenosine monophosphate-activated protein kinase.


RESULTS
Their structures were determined by comparing their nuclear magnetic resonance data with those reported in the literature. Three epidioxy sterols (3-5) showed inhibitory activities toward Foxo3a, HMGCR-GFP and NF-κB-luciferase with the IC50 values 4.9-6.8 μg/mL. The hydroperoxyl sterol 29-hydroperoxystigmasta-5,24(28)-dien-3-ol (2) had diverse inhibitory activities against Foxo3a, HMGCR-GFP, NF-κB-luciferase, PGC-1α, PTP1B and MMP, with IC50 values of 3.8-19.1 μg/mL.


CONCLUSIONS
The bioactivities of 3-5 showed that 5α,8α-epidioxy is the active group. Otherwise, the most plausible biosynthesis pathway for 1 and 2 in sponge involves the abstraction of an allylic proton by an activated oxygen, such as O2, along with migration of carbon-carbon double bond. Therefore, the bioactive and unstable steroid should be biosynthesized in sponge under a special ecological environment to act as a defensive strategy against invaders.
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences , Guangzhou , China .
Xuefeng
X
Zhou
Jianfan
J
Sun
Wanlei
W
Ma
Wei
W
Fang
Zhefan
Z
Chen
Bin
B
Yang
Yonghong
Y
Liu
D000818:Animals; D059001:Aquatic Organisms / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002681:China; D057166:High-Throughput Screening Assays; D020128:Inhibitory Concentration 50; D007448:Invertebrates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009792:Oceans and Seas; D013261:Sterols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001688:Biological Products; D013261:Sterols