{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:23:53Z","timestamp":1784690633294,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute, National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA125066"],"award-info":[{"award-number":["P01 CA125066"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"XJTLU Research Development Fund","award":["RDF-23-01-100"],"award-info":[{"award-number":["RDF-23-01-100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cardenolides are an important group of steroidal natural products and have been used successfully for the treatment of cardiovascular diseases by targeting Na+\/K+-ATPase (NKA) and found more recently to show potential anticancer activity. Biological investigations indicate that both the C-17 lactone unit and the C-3 saccharide moiety of these compounds play an important role in their interaction with NKA and in manifesting the resultant bioactivities. Interestingly, the crystal structures of several cardenolides show various conformations, due to a rotation of the C-3 saccharide moiety or the C-17 lactone unit. These rotation conformations could affect their binding to NKA and the resultant bioactivities, and thus docking profiles with NKA for several cardenolides, including cryptanoside A, digoxin and its aglycone, digoxigenin, and gitoxin, have been investigated in the present investigation. The results indicate that the binding poses of the rotation conformations of the cardenolides selected are different when they bind to NKA, as indicated by their docking scores calculated. For each compound, the rotation conformations observed could be in a dynamic equilibrium, of which each conformer may interact with NKA differentially, and these rotation conformers could act on NKA cooperatively to lead to a specific bioactivity.<\/jats:p>","DOI":"10.3390\/molecules30244815","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"4815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rotation Conformational Effects of Selected Cytotoxic Cardiac Glycosides on Their Interactions with Na+\/K+-ATPase"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-1466","authenticated-orcid":false,"given":"Yulin","family":"Ren","sequence":"first","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8618-1729","authenticated-orcid":false,"given":"Peirun","family":"Yang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith C.","family":"Gallucci","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Wang","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-4610","authenticated-orcid":false,"given":"Sijin","family":"Wu","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-8707","authenticated-orcid":false,"given":"A. Douglas","family":"Kinghorn","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.biopha.2016.10.030","article-title":"Plant-derived cardiac glycosides: Role in heart ailments and cancer management","volume":"84","author":"Patel","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1124\/mi.8.1.8","article-title":"Cardiac glycosides as novel cancer therapeutic agents","volume":"8","author":"Newman","year":"2008","journal-title":"Mol. Interv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Reddy, D., Kumavath, R., Barh, D., Azevedo, V., and Ghosh, P. (2020). 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