Document Detail

Terpene conjugates of the Nigella sativa seed-oil constituent thymoquinone with enhanced efficacy in cancer cells.
MedLine Citation:
PMID:  20087986     Owner:  NLM     Status:  MEDLINE    
Thymoquinone (TQ; 1) is a weak anticancer constituent of black seed oil. Derivatives bearing terpene-terminated 6-alkyl residues were tested in cells of human HL-60 leukemia, 518A2 melanoma, multidrug-resistant KB-V1/Vbl cervix, and MCF-7/Topo breast carcinomas, as well as in non-malignant human foreskin fibroblasts. Derivatives with a short four-atom spacer between quinone and cyclic monoterpene moieties were more antiproliferative than analogues with longer spacers. 6-(Menthoxybutyryl)thymoquinone (3a) exhibited single-digit micromolar IC(50) (72 h) values in all four cell lines. It was seven times more active than TQ (1) in 518A2 melanoma cells and four times in KB-V1/Vbl cervix carcinoma cells, while only half as toxic in the fibroblasts. Compound 3a was also not a substrate for the P-gp and BCRP drug transporters of the resistant cancer cells. The caryophyllyl and germacryl conjugates 3e and 3f specifically inhibited the growth of the resistant MCF-7 breast carcinoma cells. Conjugation of TQ with the triterpene betulinic acid via the OH group as in 3g led to a loss in activity, while conjugation via the carboxylic acid afforded compound 4 with nanomolar IC(50) (72 h) activity against HL-60 cells. All anticancer-active derivatives of TQ (1) induced apoptosis associated with DNA laddering, a decrease in mitochondrial membrane potential and a slight increase in reactive oxygen species.
Katharina Effenberger; Sandra Breyer; Rainer Schobert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry & biodiversity     Volume:  7     ISSN:  1612-1880     ISO Abbreviation:  Chem. Biodivers.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-26     Completed Date:  2010-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197449     Medline TA:  Chem Biodivers     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  129-39     Citation Subset:  IM    
Organisch-chemisches Laboratorium der Universit?t Bayreuth, Universit?tsstrasse 30, NW 1, D-95447 Bayreuth.
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MeSH Terms
Antineoplastic Agents, Phytogenic / chemistry*,  isolation & purification,  pharmacology
Benzoquinones / chemistry*,  isolation & purification,  pharmacology
Cell Line, Tumor
Drug Screening Assays, Antitumor
HL-60 Cells
Membrane Potential, Mitochondrial / drug effects
Nigella sativa / chemistry*
Oils, Volatile / chemistry
Seeds / chemistry
Terpenes / chemistry*,  isolation & purification,  pharmacology
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Benzoquinones; 0/Oils, Volatile; 0/Terpenes; 490-91-5/thymoquinone

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