title: Diosgenin-based thio(seleno)ureas and triazolyl glycoconjugates as hybrid drugs. Antioxidant and antiproliferative profile.
abstract: The stereoselective preparation of diosgenin-derived thio(seleno)ureas and glycomimetics bearing a 1,2,3-triazolyl tether on C-3 has been accomplished. The key steps in the synthetic pathway are the incorporation of an amino moiety and its further transformation into thio- and selenoureas, and also a click chemistry reaction involving a propargyl residue and an azido moiety to afford carbohydrate-derived 1,2,3-triazoles; subsequent BF3-promoted acetolysis of the spiranic moiety afforded the corresponding 22-oxocholestanic structure. The N-phenyl selenourea, an hitherto unknown steroidal derivative, turned out to be a potent ROS scavenger, in particular against free radicals (EC50 = 29.47 ± 2.33 μM, DPPH method), and as a glutathione peroxidase mimic in the elimination of H2O2 (t1/2 = 4.8 min, 1% molar ratio). 22-Oxocholestane structures bearing a C-3 azido, propargyl, thioureido, and particularly selenoureido moiety behaved as strong antiproliferative agents against HeLa cells (IC50 1.87-11.80 μM). N-phenyl selenourea also exhibited IC50 values lower than 6.50 μM for MDA-MB-231, MCF-7 and HepG2 cancer cells; apoptosis was found to be involved in its mode of action. Such compound was also capable of efficiently eliminating ROS endogenously produced by HeLa cells. Antiproliferative properties of thioxo and selenoxo derivatives were stronger than diosgenin.
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Romero-Hernández
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico. Electronic address: penelope.merino@correo.buap.mx.
authors.forename: Penélope
authors.initials: P
authors.lastname: Merino-Montiel
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico.
authors.forename: Sara
authors.initials: S
authors.lastname: Montiel-Smith
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico.
authors.forename: Socorro
authors.initials: S
authors.lastname: Meza-Reyes
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vega-Báez
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red -Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red -Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain. Electronic address: osc-lopez@us.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: López
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006001:Glycoconjugates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D016566:Organoselenium Compounds / Q000737:chemistry*; D010851:Picrates / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014230:Triazoles / Q000737:chemistry*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D006001:Glycoconjugates; D016566:Organoselenium Compounds; D010851:Picrates; D017382:Reactive Oxygen Species; D014230:Triazoles; C081959:selenourea; D014508:Urea; C004931:1,1-diphenyl-2-picrylhydrazyl; D005979:Glutathione Peroxidase; D004144:Diosgenin
keywords: Antioxidant; Antiproliferative agent; Diosgenin; ROS scavenger; Selenoureas; Thioureas