{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:32:23Z","timestamp":1791599543810,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Cardiovascular diseases (CVDs) have become the leading cause of disability and death worldwide, particularly in low- and middle-income countries. Hypertension, a major cause of CVD progression, is widely attributable to genetic, behavioral, and environmental risk factors. Among the genetic reasons, angiotensin II enzyme, produced as a result of abnormal functioning of the renin\u2013angiotensin system, is reported as the foremost cause of hypertension. A cascade of genes, including those encoding for WNK kinases (WNK1 and WNK4), Bp1, Bp2, angiotensinogen, and other enzymes, is involved in the conversion of angiotensin I to angiotensin II. However, the angiotensin-converting enzyme (ACE) plays a crucial role in this pathway. Therefore, ACE could be a potential therapeutic target in regulating the conversion of angiotensin I to angiotensin II and eventually controlling hypertension. In this study, a molecular docking-based approach was utilized for identifying and evaluating potential inhibitors of ACE present in herbs, other natural sources, and synthetic sources, on the basis of these compounds\u2019 binding affinities and other physicochemical features. In addition, the suitability of these inhibitors as drugs for biological systems, considering their adsorption, distribution, metabolism, and excretion (ADME), was predicted using Lipinski\u2019s rule. In conclusion, our study provides a novel and clearer insight into the interaction properties of known putative inhibitors of ACE.<\/jats:p>","DOI":"10.3390\/ijerph16060923","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T04:12:09Z","timestamp":1552623129000},"page":"923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":155,"title":["A Molecular Docking Approach to Evaluate the Pharmacological Properties of Natural and Synthetic Treatment Candidates for Use against Hypertension"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-7597","authenticated-orcid":false,"given":"Syed Awais","family":"Attique","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-4590","authenticated-orcid":false,"given":"Rana Muhammad","family":"Atif","sequence":"additional","affiliation":[{"name":"Department of Plant Breeding and Genetics, University of Agriculture, Faisalabad 38040, Pakistan"},{"name":"Center for Advanced Studies in Agriculture and Food Security, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-5387","authenticated-orcid":false,"given":"Shahid","family":"Mahboob","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid A.","family":"Al-Ghanim","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-3183","authenticated-orcid":false,"given":"Muhammad","family":"Bilal","sequence":"additional","affiliation":[{"name":"School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zohaib","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Agriculture, Faisalabad 38040, Pakistan"},{"name":"Center for Advanced Studies in Agriculture and Food Security, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"ref_1","unstructured":"Mendis, S., Puska, P., Norrving, B., and World Health Organization (2011). Global Atlas on Cardiovascular Disease Prevention and Control, World Health Organization."},{"key":"ref_2","first-page":"1459","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"8","year":"2016","journal-title":"Lancet"},{"key":"ref_3","first-page":"1","article-title":"Epidemiology of cardiovascular disease in the 21st century: Updated numbers and updated facts","volume":"1","author":"Santulli","year":"2013","journal-title":"J. Cardiovasc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.aogh.2016.02.002","article-title":"Hypertension and Related Cardiovascular Disease Burden in China","volume":"82","author":"Bundy","year":"2016","journal-title":"Ann. Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/jch.12479","article-title":"Using the Global Burden of Disease study to assist development of nation-specific fact sheets to promote prevention and control of hypertension and reduction in dietary salt: A resource from the World Hypertension League","volume":"17","author":"Campbell","year":"2015","journal-title":"J. Clin. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00059-003-2516-6","article-title":"Genetics of human hypertension","volume":"28","author":"Ruppert","year":"2003","journal-title":"Herz"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/hmg\/ddi187","article-title":"Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study","volume":"14","author":"Newhouse","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/sj.ejhg.5200874","article-title":"Detection of putative functional angiotensinogen (AGT) gene variants controlling plasma AGT levels by combined segregation-linkage analysis","volume":"10","author":"Brand","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.foodchem.2010.09.048","article-title":"Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from arachin by simulated gastric digestion","volume":"125","author":"Jimsheena","year":"2011","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/gb-2003-4-8-225","article-title":"Angiotensin-I-converting enzyme and its relatives","volume":"4","author":"Riordan","year":"2003","journal-title":"Genome Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.tips.2015.03.001","article-title":"Angiotensins as therapeutic targets beyond heart disease","volume":"36","author":"Brandan","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D302","DOI":"10.1093\/nar\/gkj120","article-title":"The RCSB PDB information portal for structural genomics","volume":"34","author":"Kouranov","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1021\/bi00859a010","article-title":"Spectroscopic determination of tryptophan and tyrosine in proteins","volume":"6","author":"Edelhoch","year":"1967","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"W39","DOI":"10.1093\/nar\/gkv416","article-title":"The MEME suite","volume":"43","author":"Bailey","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"W202","DOI":"10.1093\/nar\/gkp335","article-title":"MEME SUITE: Tools for motif discovery and searching","volume":"37","author":"Bailey","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D1202","DOI":"10.1093\/nar\/gkv951","article-title":"PubChem substance and compound databases","volume":"44","author":"Kim","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1021\/ci500681r","article-title":"DOCKTITE\u2014A Highly Versatile Step-by-Step Workflow for Covalent Docking and Virtual Screening in the Molecular Operating Environment","volume":"55","author":"Scholz","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/nrd941","article-title":"Integration of virtual and high-throughput screening","volume":"1","author":"Bajorath","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1126\/science.1096361","article-title":"The many roles of computation in drug discovery","volume":"303","author":"Jorgensen","year":"2004","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0022-2836(82)90153-X","article-title":"A geometric approach to macromolecule-ligand interactions","volume":"161","author":"Kuntz","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.drudis.2011.07.006","article-title":"Structure-based drug design to augment hit discovery","volume":"16","author":"Kalyaanamoorthy","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_23","unstructured":"Chemical Computing Group Inc. (2016). Molecular Operating Environment (MOE), Chemical Computing Group Inc.. H3A 2R7."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1021\/ci7001473","article-title":"2D depiction of protein\u2013ligand complexes","volume":"47","author":"Clark","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2174\/156802608786786624","article-title":"Medicinal chemistry and the molecular operating environment (MOE): Application of QSAR and molecular docking to drug discovery","volume":"8","author":"Vilar","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_26","first-page":"1158","article-title":"In silico screening of chemical compounds from roselle (Hibiscus Sabdariffa) as angiotensin-I converting enzyme inhibitor used PyRx program","volume":"3","author":"Yuliana","year":"2013","journal-title":"ARPN J. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/prot.10465","article-title":"Improved protein\u2013ligand docking using GOLD","volume":"52","author":"Verdonk","year":"2003","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/jm020406h","article-title":"Surflex: Fully automatic flexible molecular docking using a molecular similarity-based search engine","volume":"46","author":"Jain","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/prot.20217","article-title":"FlexX-Scan: Fast, structure-based virtual screening","volume":"57","author":"Schellhammer","year":"2004","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcc.540150503","article-title":"ICM\u2014A new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation","volume":"15","author":"Abagyan","year":"1994","journal-title":"J. Comput. Chem."},{"key":"ref_33","unstructured":"Molegro, A. (2011). MVD 5.0 Molegro Virtual Docker, CLC bio."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/prot.20149","article-title":"Comparative evaluation of eight docking tools for docking and virtual screening accuracy","volume":"57","author":"Kellenberger","year":"2004","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S1093-3263(02)00164-X","article-title":"LigandFit: A novel method for the shape-directed rapid docking of ligands to protein active sites","volume":"21","author":"Venkatachalam","year":"2003","journal-title":"J. Mol. Graph. Model."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ci6002637","article-title":"Docking ligands into flexible and solvated macromolecules. 1. Development and validation of FITTED 1.0","volume":"47","author":"Corbeil","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1021\/ci7001236","article-title":"GlamDock: Development and validation of a new docking tool on several thousand protein\u2212ligand complexes","volume":"47","author":"Tietze","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hsu, K.-C., Chen, Y.-F., Lin, S.-R., and Yang, J.-M. (2011). iGEMDOCK: A graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-S1-S33"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules","volume":"11","author":"Daina","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1056\/NEJMoa0806182","article-title":"Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients","volume":"359","author":"Jamerson","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jinsphys.2017.09.007","article-title":"The angiotensin converting enzyme (ACE) inhibitor, captopril disrupts the motility activation of sperm from the silkworm, Bombyx mori","volume":"103","author":"Nagaoka","year":"2017","journal-title":"J. Insect Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jpba.2015.03.038","article-title":"Use of LC\u2013MS\/TOF, LC\u2013MSn, NMR and LC\u2013NMR in characterization of stress degradation products: Application to cilazapril","volume":"111","author":"Narayanam","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/13880209.2016.1230635","article-title":"Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats","volume":"55","author":"Younas","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e4004","DOI":"10.1002\/bmc.4004","article-title":"Structural identification of degradants of moexipril by LC-MS\/MS","volume":"31","author":"Reddy","year":"2017","journal-title":"Biomed. Chromatogr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1161\/HYPERTENSIONAHA.116.07854","article-title":"Long-term mortality in hypertensive patients with coronary artery disease: Results from the US cohort of the International Verapamil (SR)\/Trandolapril Study","volume":"68","author":"Elgendy","year":"2016","journal-title":"Hypertension"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ahj.2017.07.006","article-title":"Design for the sacubitril\/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study)","volume":"193","author":"Shaddy","year":"2017","journal-title":"Am. Heart J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ddr.21280","article-title":"Fosinopril Prevents the Development of Tactile Allodynia in a Streptozotocin-Induced Diabetic Rat Model","volume":"76","year":"2015","journal-title":"Drug Dev. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"992","DOI":"10.5740\/jaoacint.16-0279","article-title":"A Validated HPLC Method for Simultaneous Determination of Perindopril Arginine, Amlodipine, and Indapamide: Application in Bulk and in Different Pharmaceutical Dosage Forms","volume":"100","author":"Elkady","year":"2017","journal-title":"J. AOAC Int."},{"key":"ref_50","first-page":"1470320316647239","article-title":"Quinapril decreases antifibrinolytic and prooxidative potential of propofol in arterial thrombosis in hypertensive rats","volume":"17","author":"Kisiel","year":"2016","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1161\/HYPERTENSIONAHA.117.09714","article-title":"Relative and Combined Prognostic Importance of On-Treatment Mean and Visit-to-Visit Blood Pressure Variability in ONTARGET and TRANSCEND PatientsNovelty and Significance","volume":"70","author":"Mancia","year":"2017","journal-title":"Hypertension"},{"key":"ref_52","unstructured":"Reuter, H., Koch, H., and Lawson, L. (1996). The Science and Therapeutic Application of Allium sativum L. and Related Species, Williams and Wilkins."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/np9604893","article-title":"Natural products in drug discovery and development","volume":"60","author":"Cragg","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_54","first-page":"216","article-title":"Attenuation of oxidative stress, inflammation, and endothelial dysfunction in hypercholesterolemic rabbits by allicin","volume":"94","author":"Ghoneim","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/clc.4960160407","article-title":"Fosinopril monotherapy: Relationship between blood pressure reduction and time of administration","volume":"16","author":"Ford","year":"1993","journal-title":"Clin. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0008-6363(99)00239-4","article-title":"The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice","volume":"44","author":"Hayek","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Heart Outcomes Prevention Evaluation Study Investigators (2000). Effects of an angiotensin-converting\u2013enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N. Engl. J. Med., 342, 145\u2013153.","DOI":"10.1056\/NEJM200001203420301"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead-and drug-like compounds: The rule-of-five revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today Technol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.addr.2016.04.029","article-title":"Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions","volume":"101","author":"Lipinski","year":"2016","journal-title":"Adv. Drug Deliv. Rev."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/6\/923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:54Z","timestamp":1760186334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/6\/923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,14]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["ijerph16060923"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16060923","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,14]]}}}