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 .
Pharm Biol. 2014 Feb;52(2):187-90. doi: 10.3109/13880209.2013.821664. Epub 2013 Sep 30.
Epidioxy sterols and sterols with special side chains, such as hydroperoxyl sterols, usually obtained from marine natural products, are attractive for bioactivities.
To isolate and screen bioactive and special sterols from China Sea invertebrates.
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.
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.
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.
来自海洋天然产物的表环氧甾醇和具有特殊侧链的甾醇，如过氧甾醇，通常具有生物活性。
从中国海洋无脊椎动物中分离和筛选具有生物活性和特殊甾醇。
从海绵 Xestospongia testudinaria Lamarck（Petrosiidae）中分离得到两种过氧甾醇（1 和 2），从海胆 Glyptocidaris crenularis A. Agassiz（Glyptocidaridae）、海绵 Mycale sp.（Mycalidae）和柳珊瑚 Dichotella gemmacea Milne Edwards and Haime（Ellisellidae）中分离得到三种表环氧甾醇（3-5），以及一种来自 D. gemmacea 的具有 25-乙酰氧基-19-酸酯（6）的异常甾醇。通过高通量筛选，测试了它们对 Forkhead box O 3a (Foxo3a)、3-羟基-3-甲基戊二酰辅酶 A 还原酶基因荧光蛋白 (HMGCR-GFP)、核因子 kappa B (NF-κB) 荧光素酶、过氧化物酶体增殖物激活受体-γ 共激活因子 1α (PGC-1α)、蛋白酪氨酸磷酸酶 1B (PTP1B)、线粒体膜通透性 (MMP) 和腺苷单磷酸激活蛋白激酶的生物活性。
通过将其核磁共振数据与文献报道的数据进行比较，确定了它们的结构。三种表环氧甾醇（3-5）对 Foxo3a、HMGCR-GFP 和 NF-κB-荧光素酶显示出抑制活性，IC50 值为 4.9-6.8μg/mL。过氧甾醇 29-过氧甾烷-5,24(28)-二烯-3-醇（2）对 Foxo3a、HMGCR-GFP、NF-κB-荧光素酶、PGC-1α、PTP1B 和 MMP 具有多种抑制活性，IC50 值为 3.8-19.1μg/mL。
3-5 的生物活性表明 5α,8α-表环氧是活性基团。否则，海绵中 1 和 2 的最合理生物合成途径涉及在特殊生态环境中由活性氧（如 O2）夺取烯丙基质子，并伴随着碳-碳双键的迁移。因此，生物活性和不稳定的甾体应该在海绵中作为一种防御策略来合成，以抵御入侵者。
