{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:12:07Z","timestamp":1777975927899,"version":"3.51.4"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["ACAMC"],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Melanoma is a malignancy often resistant to conventional therapies, highlighting the\nneed for novel agents that effectively target tumor progression and subdue apoptotic resistance. Isothiouronium\nsalts have shown promising anticancer potential; however, their in vivo potential remains largely unexplored.\nThis study aimed to evaluate the preclinical safety and antitumor efficacy of the isothiouronium derivative ISMF08.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>C57BL\/6J mice underwent acute and repeated-dose toxicity studies to determine the maximum tolerated\ndose (MTD) of IS-MF08. Following MTD determination, melanoma-bearing mice inoculated with B16F10\ncells were treated intraperitoneally with IS-MF08 for 10 days. Tumor growth, survival, body weight, hematological\nparameters, and histopathology of liver, kidneys, and tumor tissue were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The MTD was defined as 15 mg\/kg. Repeated dosing with IS-MF08 at 12 mg\/kg was well tolerated and\npromoted tumor growth inhibition (87%) and increased survival. Treatment also attenuated weight loss and tumor-\ninduced anemia and leukocytosis. Histological analyses of tumors showed reduced neoplastic cell density\nand signs of collagen deposition. Mild histological changes in the liver and kidneys were observed at higher\ndoses, along with an isolated increase in ALT levels and a slight increase in serum creatinine. In contrast, other\nliver enzymes (AST, ALT), TB, DB, total protein, albumin, and renal function markers remained within physiological\nlimits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>Preclinical evidence suggests that IS-MF08 is a promising candidate for further development as a multitargeted\nantineoplastic compound. It has demonstrated selectivity, tumor growth inhibition, and a manageable toxicity\nprofile, positioning it as a potential therapeutic option for melanoma and possibly other solid tumors with similar\nresistance mechanisms. However, several limitations should be acknowledged. The antitumor activity of ISMF08\nwas evaluated in a single syngeneic mouse model (B16F10), which may not fully recapitulate the heterogeneity\nof human tumors. Furthermore, the lack of pharmacokinetic data and long-term toxicity assessments limits\nconclusions about the compound's safety over prolonged periods. Additionally, histopathological and hematological\nanalyses have provided initial insights into the drug's tolerability. Future studies should expand the range of tumor\nmodels, explore immunological interactions, and incorporate molecular assays and bioavailability profiles to better\nelucidate the therapeutic potential and translational applicability of IS-MF08.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>IS-MF08 demonstrated robust antitumor activity with a safety profile. Despite the limitations of the\npresent study, these findings support its continued development as a potential multi-target chemotherapeutic\nagent. Further studies are necessary to elucidate the therapeutic potential and translational applicability of ISMF08.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2174\/0118715206441663260216045255","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:24:51Z","timestamp":1777973091000},"update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Evaluation of the Methyl (Z)-2-(isothioureidomethyl)-2-pentenoate\nHydrobromide: Antitumor Efficacy and Safety Profile in a Murine Melanoma Model"],"prefix":"10.2174","volume":"26","author":[{"given":"Laura Sartori","family":"Assun\u00e7\u00e3o","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, SantaCatarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iara Fabr\u00edcia","family":"Kretzer","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas, Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970,Florian\u00f3polis, Santa Catarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Gabriela","family":"Rosa","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, SantaCatarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Martins","family":"Vernaschi","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, SantaCatarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliano Andreoli","family":"Miyake","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas, Universidade Federal de Santa Catarina (UFSC),CEP: 88040-970, Florian\u00f3polis, Santa Catarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelise Maria","family":"Nazari","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Celular, Universidade Federal de SantaCatarina (UFSC), Embriologia e Gen\u00e9tica, CEP: 88040-970, Florian\u00f3polis, Santa Catarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misael","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica,Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, Santa Catarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-1624","authenticated-orcid":true,"given":"Marcus Mandolesi","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica,Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, Santa Catarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-2948","authenticated-orcid":true,"given":"Tania Beatriz","family":"Creczynski-Pasa","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Santa Catarina (UFSC), CEP: 88040-970, Florian\u00f3polis, SantaCatarina, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","container-title":["Anti-Cancer Agents in Medicinal 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