期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 121, 期 -, 页码 120-131出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.05.029
关键词
Betulinic acid; Allobetulin; Cytotoxicity; Cell cycle; Triterpene; Activity
资金
- Czech Science Foundation [15-05620S]
- Palacky University [IGA_PrF_2015_00, IGA-PrF-2016-020, IGA_LF_2016_19]
- Technology Agency of the Czech Republic [TE01020028]
- National Sustainability Programme [LO1304]
Lupane derivatives containing an electronegative substituent in the position 2 of the skeleton are often cytotoxic, however, the most active compounds are not selective enough. To further study the influence of a substituent in the position 2 in lupane and 18 alpha-oleanane derivatives on their biological properties, we prepared a set of 38 triterpenoid compounds, 19 of them new, most of them substituted in the position 2. From betulin, we obtained 2-bromo dihydrobetulonic acid and 2-bromo allobetulon and their substitutions yielded derivatives with various substituents in the position 2 such as amines, amides, thiols, and thioethers. Nitration of allobetulon and dihydrobetulonic acid gave 2-nitro and 2,2-dinitro derivatives. Fifteen derivatives had IC50 < 50 mu M on a chemosensitive CCRF-CEM (acute lymphoblastic leukemia) cell line and were tested on another seven cancer cell lines including resistant and two non cancer lines. 2-Amino allobetulin had IC50 4.6 mu M and caused significant block of the tumor cells in S and slightly in G2/M transition and caused strong inhibition of DNA and RNA synthesis at 5 x IC50. 2-Amino allobetulin is the most active derivative of 18 alpha-oleanane skeletal type prepared in our research group to date. (C) 2016 Elsevier Masson SAS. All rights reserved.
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