{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:18:32Z","timestamp":1785327512232,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Annona macroprophyllata Donn (A. macroprophyllata) is used in traditional Mexican medicine for the treatment of cancer, diabetes, inflammation, and pain. In this work, we evaluated the antitumor activity of three acyclic terpenoids obtained from A. macroprophyllata to assess their potential as antilymphoma agents. We identified the terpenoids farnesyl acetate (FA), phytol (PT) and geranylgeraniol (Gg) using gas chromatography\u2013mass spectroscopy (GC-MS) and spectroscopic (1H, and 13C NMR) methods applied to petroleum ether extract of leaves from A. macroprophyllata (PEAm). We investigated antitumor potential in Balb\/c mice inoculated with U-937 cells by assessing brine shrimp lethality (BSL), and cytotoxic activity in these cells. In addition, to assess the potential toxicity of PEAm, FA, PT and Gg in humans, we tested their acute oral toxicity in mice. Our results showed that the three terpenoids exhibited considerable antilymphoma and cytotoxic activity. In terms of lethality, we determined a median lethal dose (LD50) for thirteen isolated products of PEAm. Gg, PT and AF all exhibited a higher lethality with values of 1.41 \u00b1 0.42, 3.03 \u00b1 0.33 and 5.82 \u00b1 0.58 \u00b5g mL\u22121, respectively. To assess cytotoxic activity against U-937 cells, we calculated the mean cytotoxic concentration (CC50) and found that FA and PT were closer in respect to the control drug methotrexate (MTX, 0.243 \u00b1 0.007 \u00b5M). In terms of antilymphoma activity, we found that FA, PT and Gg considerably inhibited lymph node growth, with median effective doses (ED50) of 5.89 \u00b1 0.39, 6.71 \u00b1 0.31 and 7.22 \u00b1 0.51 mg kg\u22121 in females and 5.09 \u00b1 0.66, 5.83 \u00b1 0.50 and 6.98 \u00b1 0.57mg kg \u22121 in males, respectively. Regarding acute oral toxicity, we classified all three terpenoids as category IV, indicating a high safety margin for human administration. Finally, in a molecular docking study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, we found binding of terpenoids to some amino acids of the catalytic site, suggesting an effect upon activity with a resulting decrease in the synthesis of intermediates involved in the prenylation of proteins involved in cancer progression. Our findings suggest that the acyclic terpenoids FA, PT, and Gg may serve as scaffolds for the development of new treatments for non-Hodgkin\u2019s lymphoma.<\/jats:p>","DOI":"10.3390\/molecules27207123","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"7123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-4366","authenticated-orcid":false,"given":"Jesica","family":"Ram\u00edrez-Santos","sequence":"first","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, Escuela Superior de Medicina, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades 2\u00b0 Piso CORSE Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-5988","authenticated-orcid":false,"given":"Fernando","family":"Calzada","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades 2\u00b0 Piso CORSE Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-9875","authenticated-orcid":false,"given":"Jessica Elena","family":"Mendieta-Wejebe","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, Escuela Superior de Medicina, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-9175","authenticated-orcid":false,"given":"Rosa Mar\u00eda","family":"Ordo\u00f1ez-Razo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Gen\u00e9tica Humana, UMAE Hospital Pediatr\u00eda, 2\u00b0 Piso, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06725, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-8721","authenticated-orcid":false,"given":"Rubria Marlen","family":"Martinez-Casares","sequence":"additional","affiliation":[{"name":"Departamento de Sistemas Biol\u00f3gicos, Universidad Aut\u00f3noma Metropolitana, Calzada del Hueso 1100, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-303X","authenticated-orcid":false,"given":"Miguel","family":"Valdes","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, Escuela Superior de Medicina, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1055\/s-2001-11504","article-title":"Anticonvulsant Properties and Bio-Guided Isolation of Palmitone from Leaves of Annona diversifolia","volume":"67","author":"Navarrete","year":"2001","journal-title":"Planta Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s43450-020-00014-8","article-title":"Evaluation of acute oral toxicity, brine shrimp lethality, and antilymphoma activity of geranylgeraniol and Annona macroprophyllata Leaf extracts","volume":"30","author":"Calzada","year":"2020","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_3","unstructured":"Ballesteros, G., Rodr\u00edguez, L., De la Paz, R., Zvala, F., Urieta, M., Ballesteros, N., and Martinez, J. (2010). 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