Design, Synthesis, and Evaluation of Novel Phenolic Acid/Dipeptide/Borneol Hybrids as Potent Angiotensin Converting Enzyme (ACE) Inhibitors with Anti-hypertension Activity

Abstract

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 N-terminal and C-terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel phenolic acid/dipeptide/borneol hybrids 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—7a and 7g—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.

Design, Synthesis, and Biological Activity Evaluation of Novel AZT and Adenosine-Derived 1,2,3-Triazoles

“…As far as we know, ACE2 is a potential binding site for the virus spike protein of SAR-CoV-2 and plays a vital role in the SAR-CoV-2 infection [48], while 3CL pro is essential for SAR-CoV-2 replication but has not been present in host cells [49]. Tus, ACE2 and 3CL pro have recently emerged as excellent targets for the design of anticoronaviral compounds [49,50]. For screening of both ACE2 and 3CL pro inhibitory activities, fve adenosine triazole derivatives 11a, 11h, 11i, 11m, and 11q are selected for these tests.…”

Correction: Sun, Y.; et al. Design, Synthesis, and Evaluation of Novel 2-Hydroxypyrrolobenzodiazepine-5,11-dione Analogues as Potent Angiotensin Converting Enzyme (ACE) Inhibitors. Molecules 2017, 22, 1739

“…The author wishes to make the following corrections to this paper [ 1 ]. Due to our oversight, the title of article [ 1 ] was same as that of article [ 2 ].…”

“…The author wishes to make the following corrections to this paper [ 1 ]. Due to our oversight, the title of article [ 1 ] was same as that of article [ 2 ]. Because our research ideas and methods were different from those of article [ 2 ], we did not list it as a reference study in the article [ 1 ].…”

“…Due to our oversight, the title of article [ 1 ] was same as that of article [ 2 ]. Because our research ideas and methods were different from those of article [ 2 ], we did not list it as a reference study in the article [ 1 ]. We would like to offer our sincere apologies to all of the authors of the article [ 2 ], who were Addla Dinesh, Jallapally Anvesh, Kanwal Abhinav, Sridhar Balasubramanian, Banerjee Sanjay K., and Kantevari Srinivas.…”