期刊
NEOPLASMA
卷 56, 期 4, 页码 321-330出版社
VEDA, SLOVAK ACAD SCIENCES
DOI: 10.4149/neo_2009_04_321
关键词
nitrogen mustard; indole phytoalexin; methoxyspirobrassinol; DNA-damaging compounds; drug resistance
类别
资金
- Slovak Research and Development Agency [APVV-0514-06]
- Slovak Grant Agency for Science [1/3553/06]
Nitrogen mustards cis-1-methoxy-2-deoxy-2-[N,N-bis(2'-chloroethyl)amino]spirobrassinol (4) and trans-1-methoxy-2-deoxy-2-[N,N-bis(2'-chloroethyl)amino]spirobrassinol (5) derived from 1-methoxyspirobrassinol, an indole phytoalexin produced by the Japanese radish Raphanus sativus var. hortensis were designed as prospective dual-action compounds with DNA-alkylating effect and glutathione-depleting effects that may sensitize cancer cells to alkylating agents. Both new compounds demonstrated cytostatic/cytotoxic effects on various leukemia and ovarian cancer cell lines and dsDNA-destabilizing effects in vitro. Compound 4, the more promising of the two compounds, exerts earlier onset of anticancer effects on Jurkat cells via induction of apoptosis compared to the traditional alkylating anticancer agent melphalan. In addition, it demonstrated higher potency on ovarian cancer OVCAR-3 cell line and lower fold resistance between Jurkat and Jurkat-M cells selected for the resistance to melphalan. Therefore, compound 4 may be less affected by certain cancer drug resistance mechanisms than melphalan and it may become a prototype of a new class of anticancer active nitrogen mustards that combine DNA-damaging and DNA-damage-sensitizing properties.
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