{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T17:16:37Z","timestamp":1775927797753,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"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>Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin\u2019s lymphoma.<\/jats:p>","DOI":"10.3390\/molecules29091956","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T05:26:13Z","timestamp":1714022773000},"page":"1956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico"],"prefix":"10.3390","volume":"29","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-8166","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Vel\u00e1zquez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, Escuela Nacional de Medicina y Homeopat\u00eda, Av. Guillermo Massieu Helguera 239, La Pur\u00edsima Ticoman, Gustavo A. Madero, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal","family":"Arg\u00fcello-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. Instituto Polit\u00e9cnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"\u00c1rea Acad\u00e9mica de Farmacia, Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Km 4.5, Carretera Pachuca-Tulancingo, Unidad Universitaria, Pachuca 42076, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-7922","authenticated-orcid":false,"given":"Elizabeth","family":"Barbosa","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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.indcrop.2010.06.012","article-title":"Chemical composition, color, and antioxidant activity of three varieties of Annona diversifolia Safford fruits","volume":"34","year":"2011","journal-title":"Ind. Crops Prod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brindis, F., Gonz\u00e1lez-Trujano, M.E., Gonz\u00e1lez-Andrade, M., Aguirre-Hern\u00e1ndez, E., and Villalobos-Molina, R. (2013). Aqueous extract of Annona macroprophyllata: A potential a-glucosidase inhibitor. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/591313"},{"key":"ref_3","first-page":"137","article-title":"Producci\u00f3n de ilama (Annona diversifolia Saff.) en el tr\u00f3pico seco de Guerrero, M\u00e9xico","volume":"12","year":"2006","journal-title":"Rev. Chapingo Ser. Hortic."},{"key":"ref_4","first-page":"337","article-title":"Linking local Appreciation with conservation of an edible fruit species: The case study of Ilama (Annona diversifolia Saff.) in Tierra Caliente, Mexico","volume":"9","author":"Lefebvre","year":"2018","journal-title":"Nat. Resour."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1055\/s-2006-931598","article-title":"Palmitone isolated from Annona diversifolia induces an anxiolytic-like effect in mice","volume":"72","author":"Navarrete","year":"2006","journal-title":"Plant Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Santos, J., Calzada, F., Mendieta-Wejebe, J.E., Ordo\u00f1ez-Razo, R.M., Martinez-Casares, R.M., and Valdes, M. (2022). Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies. Molecules, 27.","DOI":"10.3390\/molecules27207123"},{"key":"ref_7","unstructured":"World Health Organization (2023, February 22). Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_8","unstructured":"World Health Organization (2023, August 25). Available online: https:\/\/www.iarc.who.int\/news-events\/latest-global-cancer-data-cancer-burden-rises-to-19-3-million-new-cases-and-10-0-million-cancer-deaths-in-2020\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/bs.acc.2019.11.002","article-title":"New biomarkers in non-Hodgkin lymphoma and acute leukemias","volume":"96","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_10","unstructured":"International Agency for Research on Cancer (2023, August 30). GLOBOCAN 2020. Global Cancer Observatory. Available online: https:\/\/gco.iarc.fr\/today\/data\/factsheets\/cancers\/34-Non-hodgkin-lymphoma-fact-sheet.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s11899-015-0267-0","article-title":"To each its own: Linking the biology and epidemiology of NHL subtypes","volume":"10","author":"Koff","year":"2015","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Omari, N., Bakrim, S., Bakha, M., Lorenzo, J.M., Rebezov, M., Shariati, M.A., and Bouyahya, A. (2021). Natural bioactive compounds targeting epigenetic pathways in cancer: A review on alkaloids, terpenoids, quinones, and isothiocyanates. Nutrients, 13.","DOI":"10.3390\/nu13113714"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.jep.2010.11.055","article-title":"Mexican medicinal plants used for cancer treatment: Pharmacological, phytochemical and ethnobotanical studies","volume":"133","author":"Villarreal","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s10495-021-01684-y","article-title":"Terpenoids\u2019 anti-cancer effects: Focus on autophagy","volume":"26","author":"Baassiri","year":"2021","journal-title":"Apoptosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00005-007-0039-1","article-title":"Terpenes: Substances useful in human healthcare","volume":"55","author":"Paduch","year":"2007","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.31768\/2312-8852.2016.38(3):158-168","article-title":"Insights into the mechanism of natural terpenoids as NF-\u03baB inhibitors: An overview on their anticancer potential","volume":"38","author":"Jain","year":"2016","journal-title":"Exp. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.1099320","article-title":"The pathophysiology of mitochondrial cell death","volume":"305","author":"Green","year":"2004","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/17474086.2017.1303374","article-title":"Targeting indolent non-Hodgkin lymphoma","volume":"10","author":"Leslie","year":"2017","journal-title":"Expert Rev. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100672","DOI":"10.1016\/j.blre.2020.100672","article-title":"Targeting MCL-1 in hematologic malignancies: Rationale and progress","volume":"44","author":"Wei","year":"2020","journal-title":"Blood Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.humpath.2004.04.018","article-title":"MCL-1 expression in B-cell non-Hodgkin\u2019s lymphomas","volume":"35","author":"Rassidakis","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16213","DOI":"10.18632\/oncotarget.23806","article-title":"An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma","volume":"9","author":"Li","year":"2018","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sangande, F., Julianti, E., and Tjahjono, D.H. (2020). Ligand-based pharmacophore modeling, molecular docking, and molecular dynamic studies of dual tyrosine kinase inhibitor of EGFR and VEGFR2. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207779"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1593\/neo.121962","article-title":"The role of angiogenesis in human non-Hodgkin lymphomas","volume":"15","author":"Ribatti","year":"2013","journal-title":"Neoplasia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1007\/s11033-019-05080-3","article-title":"In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line","volume":"46","author":"Moradipoodeh","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nm.3048","article-title":"ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets","volume":"19","author":"Souers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1021\/jm501258m","article-title":"Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity","volume":"58","author":"Bruncko","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1016\/j.bmcl.2013.03.042","article-title":"Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach","volume":"23","author":"Sanphanya","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.biopha.2018.06.131","article-title":"Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity","volume":"106","author":"Babaei","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kamran, S., Sinniah, A., Abdulghani, M.A., and Alshawsh, M.A. (2022). Therapeutic potential of certain terpenoids as anticancer agents: A scoping review. Cancers, 14.","DOI":"10.3390\/cancers14051100"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cox-Georgian, D., Ramadoss, N., Dona, C., and Basu, C. (2019). Therapeutic and medicinal uses of terpenes. Med. Plants, 333\u2013359.","DOI":"10.1007\/978-3-030-31269-5_15"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1634\/theoncologist.2015-0164","article-title":"Preventing and managing toxicities of high-dose methotrexate","volume":"21","author":"Howard","year":"2016","journal-title":"Oncologist"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48336","DOI":"10.1039\/C5RA24464A","article-title":"Extraction and purification of phytol from Abutilon indicum: Cytotoxic and apoptotic activity","volume":"6","author":"Thakor","year":"2016","journal-title":"RSC Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/ptr.5342","article-title":"Activation of caspase-9\/3 and inhibition of epithelial mesenchymal transition are critically involved in antitumor effect of phytol in hepatocellular carcinoma cells","volume":"29","author":"Kim","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1177\/1535370213492693","article-title":"Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase","volume":"238","author":"Fernandes","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1080\/01635581.2017.1299876","article-title":"Synergistic impact of d-\u03b4-tocotrienol and geranylgeraniol on the growth and HMG CoA reductase of human DU145 prostate carcinoma cells","volume":"69","author":"Yeganehjoo","year":"2017","journal-title":"Nutr. Cancer."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jss.2008.04.021","article-title":"Plaunotol and geranylgeraniol induce caspase-mediated apoptosis in colon cancer","volume":"153","author":"Yoshikawa","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/oxfordjournals.jbchem.a124695","article-title":"Geranylgeraniol is a potent inducer of apoptosis in tumor cells","volume":"117","author":"Ohizumi","year":"1995","journal-title":"J. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.biopha.2018.06.035","article-title":"Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential","volume":"105","author":"Sakthivel","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","unstructured":"Song, Y., and Cho, S.K. (2015). Phytol induces apoptosis and ROS-mediated protective autophagy in human gastric adenocarcinoma AGS cells. Biochem. Analytic. Biochem., 4."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.phymed.2018.05.001","article-title":"Synergistic interaction of \u03b2-caryophyllene with aromadendrene oxide 2 and phytol induces apoptosis on skin epidermoid cancer cells","volume":"47","author":"Pavithra","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s10495-006-7979-5","article-title":"Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K 2 trigger apoptosis in human ovarian cancer TYK-nu cells","volume":"11","author":"Sonoda","year":"2006","journal-title":"Apoptosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1038\/onc.2008.301","article-title":"JNK signaling in apoptosis","volume":"27","author":"Dhanasekaran","year":"2008","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2017.05.023","article-title":"ROS signaling in the biology of cancer","volume":"80","author":"Moloney","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2559.2002.01418.x","article-title":"Tumours of histiocytes and accessory dendritic cells: An immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases","volume":"41","author":"Pileri","year":"2002","journal-title":"Histopathology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/01926230600867727","article-title":"Normal structure, function, and histology of lymph nodes","volume":"34","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1016\/j.bbamcr.2013.06.001","article-title":"Crosstalk between apoptosis, necrosis and autophagy","volume":"1833","author":"Nikoletopoulou","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s13000-015-0450-6","article-title":"Discordant lymphoma consisting of mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes: A case report","volume":"10","author":"Zhang","year":"2015","journal-title":"Diagn. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1038\/sj.cdd.4401448","article-title":"Early work on the role of mitochondria in apoptosis, an interview with Guido Kroemer","volume":"11","author":"Kroemer","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1593","DOI":"10.1038\/cddis.2014.525","article-title":"MCL-1 and BCL-xL- dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K\/AKT\/mTOR activation in lymphoid malignancies","volume":"6","author":"Choundry","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1182\/blood.2020006785","article-title":"BCL2 and MCL1 inhibitors for hematologic malignancies","volume":"138","author":"Roberts","year":"2021","journal-title":"Blood"},{"key":"ref_51","unstructured":"Norma Oficial Mexicana (2022, April 09). NOM-062-ZOO-1999: Especificaciones T\u00e9cnicas Para la Producci\u00f3n, Cuidado y Uso de Los Animales de Laboratorio. Available online: https:\/\/www.fmvz.unam.mx\/fmvz\/principal\/archivos\/062ZOO.PDF."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4103\/pr.pr_90_17","article-title":"Antilymphoma potential of the ethanol extract and rutin obtained of the leaves from Schinus molle linn","volume":"10","author":"Calzada","year":"2018","journal-title":"Pharmacogn. Res."},{"key":"ref_53","unstructured":"Luna, L.G. (1968). Manual de M\u00e9todos de Tinci\u00f3n Histol\u00f3gica del Instituto de Patolog\u00eda de las Fuerzas Armadas, McGraw-Hill. [3rd ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"Autodock4 and AutodockTools4: Automated docking with selective receptor flexibility","volume":"16","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/9\/1956\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:33:34Z","timestamp":1760106814000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/9\/1956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,24]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["molecules29091956"],"URL":"https:\/\/doi.org\/10.3390\/molecules29091956","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,24]]}}}