Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin-682018, Kerala, India.
Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin-682018, Kerala, India; Department of Biosciences, Mangalore University, Mangalagangothri 574199, Karnataka State, India.
Biomed Pharmacother. 2019 Feb;110:155-167. doi: 10.1016/j.biopha.2018.11.034. Epub 2018 Nov 20.
Amphioctopus neglectus (Family: Octopodidae) is recognised as culinary delicacy in many cultures and a common sea food item on the Mediterranean and Asian coasts. Bioassay-directed fractionation of ethyl acetate/methanol extract of A. neglectus ensued in the characterisation of four previously undescribed macrocyclic lactones (1-4). These compounds exhibited potential radical-scavenging capacities (IC 0.95-1.73 mM) along with anti-hypertensive activities (IC 1.12-2.34 mM) against angiotensin converting enzyme (ACE). The optimum binding affinity of compound 2 (-9.84 kcal mol) bearing furo[1,4,8]trioxacyclohexadecine-12,19-dione moiety with ACE, along with its permissible hydrophobic-hydrophilic balance, manifested towards its greater anti-hypertensive activity compared to other analogues. The compound 2, with lesser values of the inhibitory constant (K = 1.0 mM) towards ACE, was found to bind more effectively to the enzyme in a non-competitive manner, and could describe the greater inhibitory ramifications than those displayed by other compounds (K >1.1 mM). The ex-vivo studies revealed that compound 2 imparted protective effects against angiotensin-II induced cardiac hypertrophy at 25 μg mL on H9C2 cell lines, wherein about 34 percent decrease in cell area with increase in viability could be attributed to anti-hypertrophic effects of the compound administrated. These results confirmed that the protective effect of the isolated macrocyclic lactones is mediated by enhancement of anti-oxidant defense systems, which subsequently attenuates the hypertensive related disorders.
neglectus（章鱼科）在许多文化中被视为美食，是地中海和亚洲沿海地区常见的海鲜。对 neglectus 的乙酸乙酯/甲醇提取物进行基于生物测定的分离，得到了四个以前未描述的大环内酯（1-4）。这些化合物表现出潜在的自由基清除能力（IC 0.95-1.73mM）和抗高血压活性（IC 1.12-2.34mM），对血管紧张素转换酶（ACE）有抑制作用。具有呋喃[1,4,8]三氧杂环己十六烷-12,19-二酮部分的化合物 2（-9.84kcal/mol）的最佳结合亲和力，以及其允许的疏水性-亲水性平衡，表明其具有比其他类似物更大的抗高血压活性。与其他类似物相比，化合物 2 对 ACE 的抑制常数（K=1.0mM）值较小，以非竞争性方式更有效地与酶结合，并且可以描述比其他化合物（K>1.1mM）更大的抑制作用。离体研究表明，化合物 2 在 H9C2 细胞系上以 25μg mL 的浓度对血管紧张素 II 诱导的心肌肥厚具有保护作用，其中细胞面积减少约 34%，活力增加，这归因于该化合物的抗肥厚作用。这些结果证实，分离的大环内酯的保护作用是通过增强抗氧化防御系统来介导的，这随后减轻了与高血压相关的疾病。
