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Among all target compounds at 1\u00a0\u03bcM, compounds\n                    <jats:bold>9d<\/jats:bold>\n                    ,\n                    <jats:bold>9f<\/jats:bold>\n                    ,\n                    <jats:bold>9k<\/jats:bold>\n                    ,\n                    <jats:bold>9m<\/jats:bold>\n                    , and\n                    <jats:bold>9n<\/jats:bold>\n                    , with a protection ratio exceeding 30%, exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A. Meanwhile, compounds\n                    <jats:bold>9k<\/jats:bold>\n                    ,\n                    <jats:bold>9m<\/jats:bold>\n                    , and\n                    <jats:bold>9o<\/jats:bold>\n                    showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte, all with a dpHi\/min value less than 0.23. What is more, compounds\n                    <jats:bold>9k<\/jats:bold>\n                    ,\n                    <jats:bold>9m<\/jats:bold>\n                    ,\n                    <jats:bold>9o<\/jats:bold>\n                    and buthutin A all exhibited the specificity on NHE-1 inhibition. Molecular modelling studies suggested the ability of compounds\n                    <jats:bold>9m<\/jats:bold>\n                    and\n                    <jats:bold>9o<\/jats:bold>\n                    to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1, but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A. The structure\u2013activity relationship (SAR) studies suggested that the presences of amide group, four-carbon linker, and\n                    <jats:italic>para<\/jats:italic>\n                    hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions. This research would open new avenues for developing amide-guanidine-based cardioprotective agents.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13659-025-00497-9","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:13:19Z","timestamp":1738714399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, synthesis and biological evaluation of buthutin derivatives as cardioprotective agents"],"prefix":"10.1007","volume":"15","author":[{"given":"Yuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Hao","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Han","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Sheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yue","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Bo","family":"Gou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-3915","authenticated-orcid":false,"given":"Yu-Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"497_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yexmp.2019.01.007","volume":"107","author":"AJ Medina","year":"2019","unstructured":"Medina AJ, Pinilla OA, Portiansky EL, Caldiz CI, Ennis IL, et al. 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