New selenosteroids as antiproliferative agents

被引:42
作者
Fuentes-Aguilar, Alma [1 ]
Romero-Hernandez, Laura L. [1 ]
Arenas-Gonzalez, Ailed [1 ]
Merino-Montiel, Penelope [1 ]
Montiel-Smith, Sara [1 ]
Meza-Reyes, Socorro [1 ]
Luis Vega-Baez, Jose [1 ]
Plata, Gabriela B. [2 ]
Padron, Jose M. [2 ]
Lopez, Oscar [3 ]
Fernandez-Bolanos, Jose G. [3 ]
机构
[1] Benemerita Univ Autonoma Puebla, Fac Ciencias Quim, Ciudad Univ, Puebla 72570, Pue, Mexico
[2] Univ La Laguna, BioLab, IUBO AG, Ctr Invest Biomed Canarias CIBICAN, C Astrofis Francisco Sanchez 2, E-38206 San Cristobal la Laguna, Spain
[3] Univ Seville, Fac Quim, Dept Quim Organ, Apartado 1203, E-41071 Seville, Spain
关键词
CELL-CYCLE ARREST; BIOLOGICAL EVALUATION; ANTIOXIDANT ACTIVITY; SELENOUREAS; DERIVATIVES; ISOSELENOCYANATES; CYTOTOXICITY; MOLECULES; HECOGENIN; CHALCOGEN;
D O I
10.1039/c7ob00458c
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Starting from natural steroids (diosgenin, hecogenin, smilagenin, estrone), we have prepared a wide panel of selenoderivatives, including benzoselenazolones, selenosemicarbazones, isoselenocyanates, selenoureas, selenocyanates and diselenides, with the aim of developing new families of potential chemotherapeutic agents. The modification of the organoselenium moieties, and their position on the steroid provided valuable information concerning the antiproliferative activities. Among all the families accessed herein, the best profile was achieved for selenoureas on the A ring of estrone, which exhibited GI50 values in the range 2.0-4.1 mu M for all the tested tumor cell lines, with increased potency compared with commonly used chemotherapeutic agents, like 5-fluorouracil and cisplatin. Cell cycle analysis revealed that selenoureas induced accumulation of cells in the G1 phase of the cell cycle in the breast cancer cell lines HBL-100 and T-47D; therefore, a different mechanism than cisplatin, that induces cell cycle accumulation in the S phase as a result of DNA damage, must be involved. In the rest of the tumor cells, a slight increase of the S compartment was observed. Moreover, selenosteoids turned out to be excellent glutathione peroxidase (GPx) mimics for the catalytic removal of deleterious H2O2 (t(1/2) 8.0-22.5 min) and alkyl peroxides (t(1/2) 23.0-38.9 min) when used in substoichiometric amounts (1% molar ratio), thus providing a valuable tool for reducing the intrinsic oxidative stress in tumor progression.
引用
收藏
页码:5041 / 5054
页数:14
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