Diosgenin-based thio(seleno)ureas and triazolyl glycoconjugates as hybrid drugs. Antioxidant and antiproliferative profile.

Autor: Romero-Hernández LL; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico., Merino-Montiel P; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico. Electronic address: penelope.merino@correo.buap.mx., Montiel-Smith S; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico., Meza-Reyes S; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico., Vega-Báez JL; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, PUE, Mexico., Abasolo I; 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., Schwartz S Jr; 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., López Ó; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain. Electronic address: osc-lopez@us.es., Fernández-Bolaños JG; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2015 Jun 24; Vol. 99, pp. 67-81. Date of Electronic Publication: 2015 May 14.
DOI: 10.1016/j.ejmech.2015.05.018
Abstrakt: 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.
(Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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