{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:21:01Z","timestamp":1790619661011,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Malaysia","award":["NMRR-22-01830-PGK; 22-034"],"award-info":[{"award-number":["NMRR-22-01830-PGK; 22-034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite many publications related to the identification of new angiotensin-I-converting enzyme (ACE) inhibitors, especially peptides from natural products, the actual reason\/s for why new ACE inhibitors need to be discovered are yet to be fully understood. New ACE inhibitors are pivotal to address serious side effects caused by commercially available ACE inhibitors in hypertensive patients. Despite the effectiveness of commercial ACE inhibitors, due to these side effects, doctors often prescribe angiotensin receptor blockers (ARBs). Recent evidence has shown the benefits of ACE inhibitors over ARBs in hypertensive patients and hypertensive\u2013diabetes mellitus patients. In order to address these side effects, the somatic ACE\u2019s enzyme structures need to be revisited. The peptides isolated from the natural products need to be verified for their stability against ACE and several important gastrointestinal enzymes. The stable peptides sequence with the presence of favourable ACE inhibitory-related amino-acids, such as tryptophan (W), at the C-terminal need to be subjected to molecular docking and dynamics analyses for selecting ACE inhibitory peptide\/s with C-domain-specific inhibition instead of both C- and N-domains\u2019 inhibition. This strategy will help to reduce the accumulation of bradykinin, the driving factor behind the formation of the side effects.<\/jats:p>","DOI":"10.3390\/molecules28114532","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T02:18:29Z","timestamp":1685931509000},"page":"4532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients\u2019 Real Problems: Chronic Dry Cough and Angioedema"],"prefix":"10.3390","volume":"28","author":[{"given":"Sivananthan","family":"Manoharan","sequence":"first","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.2174\/092986712799034950","article-title":"Structure based drug design of angiotensin-I converting enzyme inhibitors","volume":"19","author":"Anthony","year":"2012","journal-title":"Curr. Med. 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