Design, Synthesis, and Cytotoxic Activity of Michael Acceptors and Enol Esters in the Benzo[b]acronycine Series
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- Doan Thi Mai Huong
- Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. n°8638, Faculté des Sciences Pharmaceutiques et Biologiques
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- Gaslonde Thomas
- Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. n°8638, Faculté des Sciences Pharmaceutiques et Biologiques
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- Michel Sylvie
- Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. n°8638, Faculté des Sciences Pharmaceutiques et Biologiques
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- Koch Michel
- Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. n°8638, Faculté des Sciences Pharmaceutiques et Biologiques
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- Tillequin François
- Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. n°8638, Faculté des Sciences Pharmaceutiques et Biologiques
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- Bailly Christian
- INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL
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- David-Cordonnier Marie-Hélène
- INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL
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- Pfeiffer Bruno
- Institut de Recherches Servier, Division Recherche Cancérologie
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- Léonce Stéphane
- Institut de Recherches Servier, Division Recherche Cancérologie
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- Pierré Alain
- Institut de Recherches Servier, Division Recherche Cancérologie
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Description
A series of 2-acyl-6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (4—6) was prepared by treatment of 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one (3) with an excess of an appropriate acyl chloride in the presence of aluminum chloride. Treatment of (±)-cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (9, 10) or (±)-cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (2, 11) with hydrochloric acid gave the corresponding 2-acyloxy-6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones, exemplified by acetate 7 and butyrate 8. None of the Michael acceptors 4—6 showed significant antiproliferative activity. Enol esters 7 and 8 were markedly cytotoxic toward L1210 leukemia cells, with IC50 values within the same range of magnitude as (±)-cis-1,2-diacetoxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one (S23906-1), currently under phase I clinical trials. In contrast with S23906-1, enol esters 7 and 8 were not reactive toward purified DNA.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 53 (8), 919-922, 2005
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204171329664
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- NII Article ID
- 10016655681
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 7372964
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- PubMed
- 16079520
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed