{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:30:01Z","timestamp":1767839401347,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia","award":["ISP20-3"],"award-info":[{"award-number":["ISP20-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Acetylcholinesterase (AChE) inhibitors and calcium channel blockers are considered effective therapies for Alzheimer\u2019s disease. AChE plays an essential role in the nervous system by catalyzing the hydrolysis of the neurotransmitter acetylcholine. In this study, the inhibition of the enzyme AChE by Sarcorucinine-D, a pregnane type steroidal alkaloid, was investigated with experimental enzyme kinetics and molecular dynamics (MD) simulation techniques. Kinetics studies showed that Sarcorucinine-D inhibits two cholinesterases\u2014AChE and butyrylcholinesterase (BChE)\u2014noncompetitively, with Ki values of 103.3 and 4.66 \u00b5M, respectively. In silico ligand-protein docking and MD simulation studies conducted on AChE predicted that Sarcorucinine-D interacted via hydrophobic interactions and hydrogen bonds with the residues of the active-site gorge of AChE. Sarcorucinine-D was able to relax contractility concentration-dependently in the intestinal smooth muscles of jejunum obtained from rabbits. Not only was the spontaneous spasmogenicity inhibited, but it also suppressed K+-mediated spasmogenicity, indicating an effect via the inhibition of voltage-dependent Ca2+ channels. Sarcorucinine-D could be considered a potential lead molecule based on its properties as a noncompetitive AChE inhibitor and a Ca2+ channel blocker.<\/jats:p>","DOI":"10.3390\/molecules27113361","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T03:16:55Z","timestamp":1653362215000},"page":"3361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sarcorucinine-D Inhibits Cholinesterases and Calcium Channels: Molecular Dynamics Simulation and In Vitro Mechanistic Investigations"],"prefix":"10.3390","volume":"27","author":[{"given":"Asaad","family":"Khalid","sequence":"first","affiliation":[{"name":"Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia"},{"name":"Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P.O. Box 2424, Khartoum 11111, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-5547","authenticated-orcid":false,"given":"Mohnad","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-6375","authenticated-orcid":false,"given":"Maria","family":"Saeed","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine & Drug Research, University of Karachi, Karachi 75530, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0210-5108","authenticated-orcid":false,"given":"Muhammad Nabeel","family":"Ghayur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Pikeville, Pikeville, KY 41501, USA"},{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surya Kant","family":"Kalauni","sequence":"additional","affiliation":[{"name":"Central Department of Chemistry, Tribhuvan University, Kirtipur 44618, Nepal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Albratty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan A.","family":"Alhazmi","sequence":"additional","affiliation":[{"name":"Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia"},{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Ahmed","family":"Mesaik","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anwarul Hassan","family":"Gilani","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"},{"name":"Department of Public Health and Nutrition, University of Haripur, Haripur 22620, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-8711","authenticated-orcid":false,"given":"Zaheer","family":"Ul-Haq","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine & Drug Research, University of Karachi, Karachi 75530, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1126\/science.275.5300.630","article-title":"Alzheimer\u2019s disease: Genotypes, phenotypes, and treatments","volume":"275","author":"Selkoe","year":"1997","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1111\/j.1471-4159.2004.02422.x","article-title":"Glycogen synthase kinase 3: A drug target for CNS therapies","volume":"89","author":"Bhat","year":"2004","journal-title":"J. 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