Central Marine Fisheries Research Institute, Cochin, Kerala, India.
Department of Chemistry, Mangalore University, Mangalagangothri, Karnataka, India.
Nat Prod Res. 2022 Aug;36(15):3786-3795. doi: 10.1080/14786419.2021.1887177. Epub 2021 Feb 23.
Angiotensin-I converting enzyme catalyses the rate-determined step of the conversion of angiotensin-I to angiotensin-II that narrows the blood vessels, and angiotensin-I converting enzyme inhibitors were recognised as important medications for hypertension-related diseases. Chemical investigation of angiotensin-I converting enzyme inhibitors from marine demospongiae (family Microcionidae), resulted in a previously undescribed 22-membered macrocyclic lactone derivative, named as clathriolide. The studied compound showed potential angiotensin converting enzyme attenuation property (IC 0.41 mM), which was comparable with the standard captopril (IC 0.36 mM). Clathriolide revealed significantly greater antioxidant potentials against free radical species (IC < 1 mM) in comparison with the standard -tocopherol (IC > 1.5 mM). Superior electronic characteristics (topological polar surface area > 100) coupled with relatively smaller binding energy and docking score of clathriolide with the aminoacyl residues of angiotensin-I converting enzyme (-11.5 and -12.2 kcal/mol, respectively) described its potential inhibitory property against angiotensin-I converting enzyme.
血管紧张素转化酶催化血管紧张素 I 转化为血管紧张素 II 的限速步骤，血管紧张素转化酶抑制剂被认为是与高血压相关疾病的重要药物。从海洋寻常海绵（Microcionidae 科）中对血管紧张素转化酶抑制剂的化学研究产生了一种以前未描述的 22 元大环内酯衍生物，命名为克拉曲内酯。所研究的化合物表现出潜在的血管紧张素转化酶衰减特性（IC 0.41mM），与标准卡托普利（IC 0.36mM）相当。与标准 -生育酚（IC > 1.5mM）相比，克拉曲内酯对自由基的抗氧化潜力明显更大（IC < 1mM）。克拉曲内酯具有优越的电子特性（拓扑极性表面积 > 100），结合其与血管紧张素转化酶的氨基酸残基的相对较小的结合能和对接评分（-11.5 和 -12.2kcal/mol），描述了其对血管紧张素转化酶的潜在抑制特性。
