Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an 710069, China.
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an 710127, China.
Molecules. 2017 Nov 3;22(11):1739. doi: 10.3390/molecules22111739.
Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide -terminal and -terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel 2-hydroxypyrrolobenzodiazepine-5,11-dione analogues were prepared and investigated for their ability to inhibit ACE. The influence of the phenolic acid and bornyl moiety on subsite selectivity is also demonstrated. Among all the new compounds, two compounds- and -reveal good inhibition potency in in vitro ACE-inhibitory tests. Interestingly, favorable binding results in molecular docking studies also supported the in vitro results. Additionally, the bioassay showed that oral administration of the two compounds displayed high and long-lasting antihypertensive activity both in acute antihypertensive tests and in therapeutic antihypertensive tests by non-invasive blood pressure measurements in spontaneously hypertensive rats.
在中药化学（CTCMC）的指导下，本研究描述了一种由酚酸和冰片部分连接到二肽末端和末端的酚酸/二肽/冰片混合体的制备。还评估了它们的血管紧张素转化酶（ACE）抑制和协同降压活性。简要地，一系列新型 2-羟基吡咯并苯并二氮杂酮-5,11-二酮类似物被制备并研究了它们抑制 ACE 的能力。还证明了酚酸和冰片部分对亚位点选择性的影响。在所有新化合物中，两种化合物-和-在体外 ACE 抑制试验中显示出良好的抑制效力。有趣的是，分子对接研究中的良好结合结果也支持了体外结果。此外，生物测定表明，两种化合物的口服给药在急性降压试验中以及通过非侵入性血压测量在自发性高血压大鼠的治疗性降压试验中均显示出高且持久的降压活性。
