Bioactivities of six sterols isolated from marine invertebrates

Abstract

Context: 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. Materials and 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-kB) luciferase, peroxisome proliferator-activated receptor-g co-activator 1a (PGC-1a), 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-kB-luciferase with the IC 50 values 4.9-6.8 mg/mL. The hydroperoxyl sterol 29-hydroperoxystigmasta-5,24(28)-dien-3-ol (2) had diverse inhibitory activities against Foxo3a, HMGCR-GFP, NF-kB-luciferase, PGC-1a, PTP1B and MMP, with IC 50 values of 3.8-19.1 mg/mL. Discussion and conclusion: The bioactivities of 3-5 showed that 5a,8a-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 O 2 , 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.

Secondary Metabolites from Gorgonian Corals of the Genus Eunicella: Structural Characterizations, Biological Activities, and Synthetic Approaches

“…Those characteristic features are often found in marine invertebrates, particularly soft corals [33,34,38,39]. The 5α,8αendoperoxides 44-51 are oxidized sterols which can be formed during photooxidation reaction by addition of an oxygen molecule to a conjugated 5,7-diene system in the precursor molecule which contains the steroidal core [40][41][42][43]. This 5α,8α-endoperoxide bond is exactly responsible for the observed biological activities [40].…”

Microbial Sterolomics as a Chemical Biology Tool

“…24-Vinyl-24-hydroperoxycholesterol 111 ( Figure 13 ) has been isolated from Xestponsgia sp. [ 33 , 86 ]. It had an IC 50 in an NF-κB-luciferase assay of 31.3 µg/mL [ 33 ] and restricted growth of various human cell lines, including A549 (IC 50 29.0 µM) and WI-38 (IC 50 43.4 µM) [ 86 ].…”

“…Isolated from a variety of fungi and sponges, as well as vascular plants, ergosterol peroxide 8 possesses broad bioactivity, including anti-tumor, immunomodulatory, inhibitory hemolytic, anti-inflammatory, antioxidant, and antimicrobial properties. Several other endoperoxides of other phytosterols and of cholestenols have been reported to have similar properties, as well [ 30 , 31 , 32 , 33 , 34 ]. Squalamine 9 is a non-microbially derived natural steroidal, which has demonstrated antimicrobial and antiangiogenic properties and has led to interest in synthetic analogues for structure-activity improvement [ 35 ].…”

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

“…with an epidioxy sterol (168) [30] after which 168 was isolated from a second Chinese Mycale sp. [126]. Another common sterol (169) was isolated from M. (Arenochalina) euplectellioides from Egypt [127].…”

“…[132]). Epidioxy sterols have shown biological activities with 168 showing toxicity against brine shrimp larvae (LD 50 value of 4.7 µg/mL [30]) and inhibitory effects against Foxo3 a (IC 50 value of 32.8 µg/mL), HMGCR-GFP (IC 50 value of 6.8 µg/mL), and NF-κB-luciferase (IC 50 value of 16.3 µg/mL) assays [126]. Mycalone (170) is a novel steroidal lactone, an unusual side chain that contains a 6-membered lactone ring has also been observed in other sterols such as 171 isolated from the root of the plant Trichodesma indicum.…”