2013年11月
Design, synthesis, and in vitro cancer cell growth inhibition evaluation and antimalarial testing of trioxanes installed in cyclic 2-enoate substructures
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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- 巻
- 69
- 号
- 開始ページ
- 294
- 終了ページ
- 309
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/j.ejmech.2013.08.008
- 出版者・発行元
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
A novel series of 1,2,4-trioxanes were synthesized from 2H-pyrans via photooxidation, and their antiproliferative and growth factor inhibitory activity has been investigated across a variety of human cancer cell lines. Compounds 5k, 51, 5s, 7a and 7c exhibited the highest activity and selectivity against a human leukemia (MV4-11) cell line (IC50 = 0.5 mu M). Compound 5o showed the highest growth factor inhibitory activity against a melanoma (LOX-IMVI) cancer cell line (GI(50) = 1.0 mu M). A SAR study has confirmed the importance of the 1,2,4-trioxane unit as a pharmacophore for anticancer activity. The computer-assisted database analysis, COMPARE, has suggested that the compounds have unique mechanisms of actions that were different from those of known anticancer drugs. Some of the selected trioxanes were tested against the NF54 strain, albeit showing weak antiplasmodial activity. The molecular docking of trioxanes and hemin reveals that a short distance (130 angstrom) leads to their physical contact. The UV-vis spectroscopic analysis ensured the definite complexation between 1,2,4-trioxanes and hemin. The role of hemin-trioxane interaction in the hemin-induced oxidative damage has been studied using methylene blue as a substrate by UV-vis spectroscopy. (C) 2013 Elsevier Masson SAS. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.ejmech.2013.08.008
- ISSN : 0223-5234
- eISSN : 1768-3254
- Web of Science ID : WOS:000330603900027