Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India.
Marine Bioprospecting Section of Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin, India; Department of Chemistry, Mangalore University, Mangalagangothri, 574199, Karnataka State, India.
Phytochemistry. 2022 Mar;195:113024. doi: 10.1016/j.phytochem.2021.113024. Epub 2021 Dec 8.
Bioactive compounds with angiotensin-I converting enzyme attenuation potential are deemed as therapeutic agents for hypertension owing to their capacity to suppress the conversion of angiotensin-I into the vasoconstrictor angiotensin-II. In an aim to develop natural angiotensin-I converting enzyme (ACE-I) inhibitors from marine algae, three 6, 6-spiroketals, spirornatas A-C were isolated from the organic extract of the spiny brown marine macroalga Turbinaria ornata (Turner) (family Sargassaceae). Spirornata A exhibited comparatively greater ACE-I attenuation potential (IC 4.5 μM) than those displayed by other studied spiroketals (IC 4.7-4.9 μM), and its activity was comparable to the ACE inhibitory agent captopril (IC 4.3 μM). Greater antioxidant properties of spirornata A against oxidants (IC 1.1-1.3 mM) also substantiated its potential attenuation property against ACE-I. Structure-activity correlation studies showed that electronic properties (topological polar surface area, 71) and balanced hydrophilic-lipophilic parameters (partition coefficient of logarithmic octanol-water ∼3.2) of spirornata A appeared to play pivotal roles in the inhibition of the targeted enzyme. Predicted drug-likeness and other physicochemical parameters appeared to attribute to the acceptable oral bioavailability of spiroketal derivatives. Additionally, the least binding energy of spirornata A with ACE-I (-10.5 kcal/mol) coupled with the maximum number of hydrogen-bonding interactions with allosteric sites of the zinc-dependent dicarboxypeptidyl peptidase could recognize its potential therapeutic application against hypertensive diseases.
具有血管紧张素转化酶抑制作用的生物活性化合物被认为是治疗高血压的药物，因为它们能够抑制血管紧张素 I 转化为血管收缩素 II。为了从海洋藻类中开发天然血管紧张素转化酶（ACE-I）抑制剂，从多刺棕色海洋大型藻类 Turbinaria ornata（特纳）（马尾藻科）的有机提取物中分离出三种 6,6-螺缩酮，即螺旋酮 A-C。螺旋酮 A 表现出比其他研究的螺缩酮（IC 4.7-4.9 μM）更大的 ACE-I 抑制潜力（IC 4.5 μM），其活性与 ACE 抑制剂卡托普利（IC 4.3 μM）相当。螺旋酮 A 对氧化剂具有更强的抗氧化性能（IC 1.1-1.3 mM），也证实了其对 ACE-I 的潜在抑制作用。构效关系研究表明，螺旋酮 A 的电子性质（拓扑极性表面积，71）和平衡的亲脂-亲水参数（对数辛醇-水分配系数∼3.2）似乎在抑制靶向酶方面起着关键作用。预测的药物相似性和其他物理化学参数似乎归因于螺缩酮衍生物的可接受的口服生物利用度。此外，螺旋酮 A 与 ACE-I 的最低结合能（-10.5 kcal/mol）加上与锌依赖性二肽基肽酶的变构位点的最大氢键相互作用数，可以识别其在治疗高血压疾病方面的潜在应用。
