Prev. Article Next Article Table of Contents

Article

Synthesis and Structure−Activity Relationships of New Benzodioxinic Lactones as Potential Anticancer Drugs

Supporting Info

Manel Romero,^† Pierre Renard,^‡ Daniel-Henry Caignard,^‡ Ghanen Atassi,^‡ Xavier Solans,^§ Pere Constans,^† Christian Bailly, and Maria Dolors Pujol*^†

Laboratori de Qumica Farmacutica (Unitat Associada al CSIC), Facultat de Farmcia, Universitat de Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain, Les Laboratoires Servier, 1 rue Carle Hebert, 92415-Courbevoie Cedex, France, Departament de Cristallografia, Mineralogia i Dipsits Minerals, Facultat de Geologia, Universitat de Barcelona, C/ Mart i Franqus s/n, 08028-Barcelona, Spain, and INSERM U-524, IRCL, Place de Verdum, 59045 Lille, France

J. Med. Chem., 2007, 50 (2), pp 294–307

DOI: 10.1021/jm061184g

Publication Date (Web): December 22, 2006

†

Laboratori de Química Farmacèutica, Facultat de Farmàcia, Universitat de Barcelona.

‡

Laboratoires Servier.

Facultat de Geologia, Universitat de Barcelona.

INSERM U-524, IRCL, Place de Verdum, 59045 Lille, France.

To whom correspondence should be addressed. Phone: 0034 93 4024534. Fax: 0034 93 4035941. E-mail: mdpujol@ub.es.

Abstract

A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity. Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationships between chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent at C-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified the potency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increased the activity. An extensive structure−activity relationship study of these derivatives, including carbon homologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds are discussed. Two lactones are recognized as potential lead compounds.

View: Full Text HTML | Hi-Res PDF

Tools

SciFinder Links

History

Published In Issue January 25, 2007
Received October 11, 2006

Recommend & Share

Related Content

Synthesis and Biological Evaluation of Novel Phenylcarbazoles as Potential Anticancer AgentsJournal of Medicinal Chemistry
- Synthesis and Biological Evaluation of Novel Phenylcarbazoles as Potential Anticancer Agents
  Sylvain Routier, Jean-Yves Mérour, Nathalie Dias, Amélie Lansiaux, Christian Bailly, Olivier Lozach, and Laurent Meijer
  Journal of Medicinal Chemistry 2006 49 (2), pp 789–799
  Abstract: We here report the synthesis and biological evaluation of new phenylcarbazole derivatives designed as potential anticancer agents. Indole and hydroxyindole were used to generate three scaffolds that were successively exploited to introduce various ...
  Abstract | Full Text HTML | Hi-Res PDF
Synthesis and Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Substituted with Nitrogen HeterocyclesJournal of Medicinal Chemistry
- Synthesis and Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Substituted with Nitrogen Heterocycles
  Muthukaman Nagarajan, Andrew Morrell, Alexandra Ioanoviciu, Smitha Antony, Glenda Kohlhagen, Keli Agama, Melinda Hollingshead, Yves Pommier, and Mark Cushman
  Journal of Medicinal Chemistry 2006 49 (21), pp 6283–6289
  Abstract: In connection with an ongoing investigation of indenoisoquinoline topoisomerase I (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing di(methoxy) and methylenedioxy substituents was held constant, and new derivatives were ...
  Abstract | Full Text HTML | Hi-Res PDF
2-Amino and 2‘-Aminocombretastatin Derivatives as Potent Antimitotic AgentsJournal of Medicinal Chemistry
- 2-Amino and 2‘-Aminocombretastatin Derivatives as Potent Antimitotic Agents
  Jang-Yang Chang, Ming-Fang Yang, Chi-Yen Chang, Chi-Ming Chen, Ching-Chuan Kuo, and Jing-Ping Liou
  Journal of Medicinal Chemistry 2006 49 (21), pp 6412–6415
  Abstract: A novel series of 2-amino and 2‘-aminocombretastatin derivatives were synthesized and evaluated for antitumor activity. Several compounds had excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 11, 20, and 21 with IC₅₀ ...
  Abstract | Full Text HTML | Hi-Res PDF

Article

Synthesis and Structure−Activity Relationships of New Benzodioxinic Lactones as Potential Anticancer Drugs

Abstract

Tools

SciFinder Links

History

Recommend & Share

Related Content

Synthesis and Biological Evaluation of Novel Phenylcarbazoles as Potential Anticancer Agents

Synthesis and Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Substituted with Nitrogen Heterocycles

2-Amino and 2‘-Aminocombretastatin Derivatives as Potent Antimitotic Agents

Other ACS content by these authors:

JOURNALS

BOOKS

MAGAZINE

COMMUNITIES

DIRECTORIES & DATABASES