{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T08:02:22Z","timestamp":1776585742664,"version":"3.51.2"},"reference-count":35,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"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>Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5\u03b1-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42\u201396% yield. Also, a new spirostanic \u03b1, \u03b2-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.<\/jats:p>","DOI":"10.3390\/molecules28217283","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T07:22:15Z","timestamp":1698304935000},"page":"7283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Synthesis of Novel aza-Steroids and \u03b1, \u03b2-Unsaturated-Cyanoketone from Diosgenin"],"prefix":"10.3390","volume":"28","author":[{"given":"Dayana","family":"Mesa","sequence":"first","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yarelys E.","family":"Augusto","sequence":"additional","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan P.","family":"Figueroa-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Coll","sequence":"additional","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-6264","authenticated-orcid":false,"given":"Andr\u00e9s F.","family":"Olea","sequence":"additional","affiliation":[{"name":"Grupo QBAB, Facultad de Ingenier\u00eda, Instituto de Ciencias Qu\u00edmicas Aplicadas, Universidad Aut\u00f3noma de Chile, Llano Subercaseaux 2801, Santiago 7500912, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidad T\u00e9cnica Federico Santa Mar\u00eda, Av. Espa\u00f1a No. 1680, Valpara\u00edso 2390123, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hern\u00e1n Astudillo","family":"Campo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Procesos Electroqu\u00edmicos, Departamento de Qu\u00edmica, Universidad del Cauca, Calle 5 No. 4-70, Popay\u00e1n 190003, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamilet","family":"Coll","sequence":"additional","affiliation":[{"name":"Center for Natural Product Researches, Faculty of Chemistry, University of Havana, Zapata and G, Vedado, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-7487","authenticated-orcid":false,"given":"Luis","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidad T\u00e9cnica Federico Santa Mar\u00eda, Av. Espa\u00f1a No. 1680, Valpara\u00edso 2390123, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10654-015-0071-0","article-title":"Trajectories of self-rated health in the last 15 years of life by cause of death","volume":"31","author":"Stenholm","year":"2016","journal-title":"Eur. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/bmt.2015.300","article-title":"Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: A study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party","volume":"51","author":"Necchi","year":"2016","journal-title":"Bone Marrow Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R10","DOI":"10.1530\/EC-18-0425","article-title":"Therapeutic advances in hormone-dependent cancers: Focus on prostate, breast and ovarian cancers","volume":"8","author":"Ulm","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1210\/edrv-11-2-221","article-title":"Endocrine Treatment of Breast Cancer in Women","volume":"11","author":"Santen","year":"1990","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2174\/092986711794480177","article-title":"Endocrine therapy of breast cancer","volume":"18","author":"Lumachi","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"\u0141ukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., and Stanis\u0142awek, A. (2021). Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers, 13.","DOI":"10.3390\/cancers13174287"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0092-8674(00)81717-1","article-title":"The structural basis of estrogen receptor\/coactivator recognition and the antagonism of this interaction by tamoxifen","volume":"95","author":"Shiau","year":"1998","journal-title":"Cell"},{"key":"ref_8","first-page":"1437","article-title":"Selective estrogen receptor modulators: Tissue specificity and clinical utility","volume":"9","author":"Martinkovich","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1021\/cr900019j","article-title":"Impact of Natural Products on Developing New Anti-Cancer Agents","volume":"109","author":"Cragg","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cbi.2015.11.006","article-title":"Cytotoxic and apoptotic effects of leptocarpin, a plant-derived sesquiterpene lactone, on human cancer cell lines","volume":"242","author":"Bosio","year":"2015","journal-title":"Chem. Biol. Inter."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18993","DOI":"10.3390\/molecules191118993","article-title":"Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines","volume":"19","author":"Montenegro","year":"2014","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.apsb.2016.06.003","article-title":"The modification of natural products for medical use","volume":"7","author":"Guo","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"172942","DOI":"10.1016\/j.ejphar.2020.172942","article-title":"Apoptotic, necrotic, and antiproliferative activity of diosgenin and diosgenin glycosides on cervical cancer cells","volume":"871","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1021\/jf000467t","article-title":"Microdetermination of Diosgenin from Fenugreek (Trigonella foenum-graecum) Seeds","volume":"48","author":"Taylor","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/10915810490499055","article-title":"Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam) root extract","volume":"23","author":"Hooker","year":"2004","journal-title":"Int. J. Toxicol."},{"key":"ref_17","first-page":"1240","article-title":"Detection and isolation of diosgenin from Costus speciosus callus raised from non-germinal seeds","volume":"2","author":"Singh","year":"2013","journal-title":"Int. J. Chem. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, P.S., Shih, Y.W., Huang, H.C., and Cheng, H.W. (2011). Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020164"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0014-5793(01)02924-6","article-title":"A plant steroid, diosgenin, induces apoptosis, cell cycle arrest and COX activity in osteosarcoma cells","volume":"506","author":"Moalic","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/01635580802357352","article-title":"Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin","volume":"61","author":"Raju","year":"2009","journal-title":"Nutr. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sethi, G., Shanmugam, M.K., Warrier, S., Merarchi, M., Arfuso, F., Kumar, A.P., and Bishayee, A. (2018). Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review. Nutrients, 10.","DOI":"10.3390\/nu10050645"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-S\u00e1nchez, L., Hern\u00e1ndez-Linares, M.G., Escobar, M.L., L\u00f3pez-Mu\u00f1oz, H., Zenteno, E., Fern\u00e1ndez-Herrera, M.A., Guerrero-Luna, G., Carrasco-Carballo, A., and Sandoval-Ram\u00edrez, J. (2016). Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines. Molecules, 21.","DOI":"10.3390\/molecules21111533"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.steroids.2016.11.003","article-title":"Synthesis and biological evaluation of novel 3-O-tethered triazoles of diosgenin as potent antiproliferative agents","volume":"118","author":"Mohammad","year":"2017","journal-title":"Steroids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111897","DOI":"10.1016\/j.ejmech.2019.111897","article-title":"Novel diosgenin derivatives containing 1,3,4-oxadiazole\/thiadiazole moieties as potential antitumor agents: Design, synthesis and cytotoxic evaluation","volume":"186","author":"Zhang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.steroids.2017.03.008","article-title":"Novel synthesis of steroidal oximes and lactams and their biological evaluation as antiproliferative agents","volume":"122","author":"Mendoza","year":"2017","journal-title":"Steroids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.ejmech.2003.09.002","article-title":"Synthesis and antineoplastic activity of 2-alkylaminoethyl derivatives of various steroidal oximes","volume":"38","author":"Jindal","year":"2003","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1016\/j.bmc.2007.05.003","article-title":"Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents","volume":"15","author":"Poza","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1515\/znb-1980-0124","article-title":"Hydroxylation of \u03945-Steroids with N-Bromosuccinimide to 5\u03b1,6\u03b2-Diols","volume":"35","author":"Dawidar","year":"1980","journal-title":"Z. F\u00fcr Naturforschung B"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Pupo, L., Zaldo-Castro, A., Exarchou, V., Tacoronte-Morales, J.E., Pieters, L., Vanden Berghe, W., Nu\u00f1ez-Figueredo, Y., and Delgado-Hern\u00e1ndez, R. (2016). In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues. Molecules, 21.","DOI":"10.3390\/molecules21080992"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.1021\/jo00171a045","article-title":"Stereospecific synthesis of selectively C-7-acetalized substituted 4a.beta.-methyl-3,4,4a,5,6,8a.alpha.-hexahydronaphthalene-1(2H),7(8H)-diones. A short total synthesis of (.+-.)-.beta.-eudesmol, (.+-.)-.beta.-selinene, and (.+-.)-.beta.-dictyopterol","volume":"48","author":"Wijnberg","year":"1983","journal-title":"J. Org. Chem."},{"key":"ref_31","unstructured":"Greene, T.W., and Wuts, P.G.M. (1991). Protective Groups in Organic Synthesis, John Wiley & Sons, Inc.. [2nd ed.]."},{"key":"ref_32","unstructured":"Sandler, S.R., and Karo, W. (1983). Organic Functional Group Preparation, John Wiley & Sons, Inc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2298\/JSC0406413K","article-title":"Photochemical and Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime","volume":"69","author":"Dabovic","year":"2004","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shoppee, C.W., and Roy, S.K. (1963). Aza-steroids. Part VI. Beckmann rearrangement of some \u03b1-hydroxy-ketoximes. J. Chem. Soc., 3774\u20133777.","DOI":"10.1039\/JR9630003774"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13379","DOI":"10.1016\/0040-4020(95)00871-5","article-title":"Synthesis and unusual beckmann fragmentation reaction of syn-3-Methoxy-6\u03b1,17\u03b2-Dihydroxyestra-1,3,5(10)-trien-7-one oxime","volume":"51","author":"Pejanovic","year":"1995","journal-title":"Tetrahedron"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/21\/7283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:12:16Z","timestamp":1760130736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/21\/7283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":35,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["molecules28217283"],"URL":"https:\/\/doi.org\/10.3390\/molecules28217283","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]}}}