{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:02:57Z","timestamp":1790154177931,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Natural products continue to provide pharmacologically relevant scaffolds for anticancer drug discovery, with alkaloids from the Amaryllidaceae family among the most structurally diverse and biologically investigated classes of plant secondary metabolites. Within this family, the Brazilian genus Griffinia\u2014comprising approximately 21 species predominantly endemic to the Atlantic Forest and Cerrado\u2014remains substantially underrepresented in the phytochemical and pharmacological literature, with fewer than five species subjected to any level of biological evaluation and no genus-wide mechanistic profile available to date. This critical review specifically examines what the current literature reports regarding the anticancer relevance of Griffinia alkaloids, addressing a gap that has not been systematically investigated in prior Amaryllidaceae reviews. Six structural classes\u2014lycorine-, galanthamine-, crinine-, hemanthamine-, montanine-, and homolycorine-type alkaloids\u2014have been detected in Griffinia species primarily through gas chromatography\u2013mass spectrometry and liquid chromatography\u2013mass spectrometry profiling; however, isolation and direct biological validation have been reported for only one species, Griffinia gardneriana, in which lycorine and related compounds exhibit cytotoxic and genotoxic activities associated with caspase-3-mediated apoptosis. This finding constitutes the sole genus-specific mechanistic anchor currently available. The broader biological literature on Amaryllidaceae alkaloids\u2014encompassing apoptosis induction, cell cycle arrest, redox imbalance, and modulation of phosphoinositide 3-kinase\/protein kinase B (PI3K\/Akt), nuclear factor kappa B (NF-\u03baB), and mitogen-activated protein kinase (MAPK) signaling\u2014is explicitly used here as contextual evidence for the structural classes detected in Griffinia, not as proof of genus-level activity. This distinction is central to the evidentiary framework of the review and is maintained throughout. Approximately 70% of evaluated Amaryllidaceae species lack comprehensive phytochemical and biological characterization, a limitation that is directly reflected in Griffinia. Future research priorities include rigorous compound isolation and structural elucidation across underexplored species, genus-specific bioactivity testing in well-defined cancer models, and mechanism-oriented studies anchored in direct experimental evidence rather than structural analogies. Semi-synthetic optimization and multi-omic approaches represent longer-term but tractable avenues once the primary pharmacological characterization is established.<\/jats:p>","DOI":"10.3390\/ijms27198466","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:14:39Z","timestamp":1790151279000},"page":"8466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alkaloids Reported in the Genus Griffinia (Amaryllidaceae): Phytochemical Evidence and Current Limitations in Anticancer Interpretation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-4550","authenticated-orcid":false,"given":"Maykon Jhuly Martins de","family":"Paiva","sequence":"first","affiliation":[{"name":"Natural Products Laboratory, Department of Pharmacy, Health Sciences School, University of Bras\u00edlia (UnB), Campus Darcy Ribeiro, Asa Norte, Brasilia 70910-900, Brazil"},{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1828-7040","authenticated-orcid":false,"given":"Caroline Priscila","family":"Furlanetto","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6916-8175","authenticated-orcid":false,"given":"Elis Ferreira","family":"Garcia","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0693-4261","authenticated-orcid":false,"given":"Layra Eugenio","family":"Pedreira","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2897-9770","authenticated-orcid":false,"given":"Walmirton Bezerra","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-9621","authenticated-orcid":false,"given":"S\u00e1via Denise Silva Carlotto","family":"Herrera","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-5290","authenticated-orcid":false,"given":"Renata Ferreira Diogo De","family":"Paiva","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3121-6643","authenticated-orcid":false,"given":"Andr\u00e9 Luiz Gomide de","family":"Morais","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Gurupi 77400-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-4947","authenticated-orcid":false,"given":"Mateus Silva","family":"Santos","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-3510","authenticated-orcid":false,"given":"Adolpho Dias","family":"Chiacchio","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Gurupi (UnirG), Para\u00edso do Tocantins Campus, Para\u00edso do Tocantins 77545-208, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-7970","authenticated-orcid":false,"given":"Taides Tavares dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Graduate Program in Animal Health and Public Health in the Tropics, Faculty of Health Sciences, Federal University of Northern Tocantins (UFNT), Aragua\u00edna 77814-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7167-7612","authenticated-orcid":false,"given":"I Made Dwi Mertha","family":"Adnyana","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi 36361, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7597-5481","authenticated-orcid":false,"given":"M\u00e1rcio","family":"Trevisan","sequence":"additional","affiliation":[{"name":"Graduate Program in Environmental Sciences, Federal University of Tocantins (UFT), Palmas 77001-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 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