{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:16:43Z","timestamp":1769818603587,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Milgrom Foundation, The Hebrew University","award":["3015001659"],"award-info":[{"award-number":["3015001659"]}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1953\/17"],"award-info":[{"award-number":["1953\/17"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bufalin and other cardiac steroids (CS) have been used for centuries for the treatment of congestive heart failure, arrhythmias, and other maladies. However, toxicity and the small therapeutic window of this family of steroids limit their use. Therefore, attempts to synthesize a potent, but less toxic, CS are of major importance. In the present study, two novel bufalin derivatives were synthesized and some of their pharmacological properties were characterized. The reaction of bufalin with Ishikawa\u2019s reagent resulted in the production of two novel bufalin derivatives: bufalin 2,3-ene and bufalin 3,4-ene. The compounds were purified with TLC and HPLC and their structure was verified with UV, NMR, and MS analyses. The biological activities of these compounds were evaluated by testing their ability to inhibit the Na+, K+-ATPase activity of the brain microsomal fraction to induce cytotoxic activity against the NCI-60 human tumor cell line panel and non-cancer human cells, and to increase the force of contraction of quail embryonic heart muscle cells in culture. The two steroids exhibited biological activities similar to those of other CS in the tested experimental systems, but with reduced cytotoxicity, advocating their development as drugs for the treatment of heart failure and arrhythmias.<\/jats:p>","DOI":"10.3390\/ijms23074007","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T09:49:41Z","timestamp":1649065781000},"page":"4007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synthesis and Biological Evaluation of Novel Bufalin Derivatives"],"prefix":"10.3390","volume":"23","author":[{"given":"VishnuPriya","family":"Sampath","sequence":"first","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noa","family":"Horesh","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Sasi","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiba","family":"Zannadeh","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Pogodin","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiv Vardan","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Lichtstein","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0031-9422(97)00426-3","article-title":"Bufadienolides from animal and plant sources","volume":"48","author":"Krenn","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2100060","DOI":"10.1002\/ardp.202100060","article-title":"Toad venom: A comprehensive review of chemical constituents, anticancer activities, and mechanisms","volume":"354","author":"Li","year":"2021","journal-title":"Arch. 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