Synthesis, Anion-Binding Properties, and In Vitro Anticancer Activity of Prodigiosin Analogues†
Jonathan L. Sessler Prof.
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorLeah R. Eller
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorWon-Seob Cho
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorSergios Nicolaou
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorApolonio Aguilar
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorJeong Tae Lee
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorVincent M. Lynch
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorDarren J. Magda Dr.
Pharmacyclics Inc. 995 E. Arques Ave, Sunnyvale, CA 94085, USA, Fax: (+1) 408-774-0340
Search for more papers by this authorJonathan L. Sessler Prof.
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorLeah R. Eller
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorWon-Seob Cho
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorSergios Nicolaou
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorApolonio Aguilar
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorJeong Tae Lee
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorVincent M. Lynch
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station–A5300, University of Texas at Austin, Austin, Texas 78712-1065, USA, Fax: (+1) 512-471-7550
Search for more papers by this authorDarren J. Magda Dr.
Pharmacyclics Inc. 995 E. Arques Ave, Sunnyvale, CA 94085, USA, Fax: (+1) 408-774-0340
Search for more papers by this authorThis work was supported by the National Institutes of Health (GM 58907). Dr. Wyeth Callaway is thanked for providing samples of pyrrole 10. We thank Ms. Beth McNally of Prof. Bradley Smith's group for her help in developing a working liposomal model membrane system.
Graphical Abstract
Pro and anti: Recognition of chloride ion and through-membrane H+/Cl− ion transport (“symport”) could account for the biological effects (anticancer activity) of prodigiosin, as inferred from model studies involving pyrrole-based anion receptors designed to mimic the key features of this naturally occurring pigment (see picture).
Supporting Information
Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z501740_s.pdf or from the author.
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1A. Fürstner, Angew. Chem. 2003, 115, 3706–3728;
10.1002/ange.200300582 Google ScholarAngew. Chem. Int. Ed. 2003, 42, 3582–3603.
- 2R. D'Alessio, A. Bargiotti, O. Carlini, F. Colotta, M. Ferrari, P. Gnocchi, A. Isetta, N. Mongelli, P. Motta, A. Rossi, M. Rossi, M. Tibolla, E. Vanotti, J. Med. Chem. 2000, 43, 2557–2565.
- 3M. S. Melvin, J. T. Tomlinson, G. Park, C. S. Day, G. R. Saluta, G. L. Kucera, R. A. Manderville, Chem. Res. Toxicol. 2002, 15, 734–741.
- 4S. B. Han, H. M. Kim, Y. H. Kim, C. W. Lee, E.-S. Jang, K. H. Son, S. U. Kim, Y. K. Kim, Int. J. Immunopharmacol. 1998, 20, 1–13.
- 5D. Yamamoto, Y. Kiyozuka, Y. Uemura, C. Yamamoto, H. Takemoto, H. Hirata, K. Tanaka, K. Hioki, A. Tsubura, J. Cancer Res. Clin. Oncol. 2000, 126, 191–197.
- 6B. Montaner, R. Perez-Toma, Life Sciences 2001, 68, 2025–2036.
- 7
- 7aM. S. Melvin, M. W. Calcutt, R. E. Noftle, R. A. Manderville, Chem. Res. Toxicol. 2002, 15, 742–748;
- 7bG. Park, J. T. Tomlinson, M. S. Melvin, M. W. Wright, C. S. Day, R. A. Manderville, Org. Lett. 2003, 5, 113–116.
- 8A. Fürstner, E. J. Grabowski, ChemBioChem 2001, 2, 706–709.
10.1002/1439-7633(20010903)2:9<706::AID-CBIC706>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- 9
- 9aT. Sato, H. Konno, Y. Tanaka, T. Kataoka, K. Nagai, H. H. Wasserman, S. Ohkuma, J. Biol. Chem. 1998, 273, 21455–21462;
- 9bS. Ohkuma, T. Sato, M. Okamoto, H. Matsuya, K. Arai, T. Kataoka, K. Nagai, H. H. Wasserman, Biochem. J. 1998, 334, 731–741.
- 10In previous work, the HCl complexes of extended “vinylogous” prodigiosin analogues,[17] a cyclic prodigiosin derivative,[18] and a phenyl-substituted dipyrromethene derivative[3] were reported. While single-point binding of chloride ion is seen in the case of the latter system, the first two structures revealed binding modes that are analogous to those seen in the case of 4⋅HCl and 7⋅HCl, respectively.
- 11During the course of preparing this manuscript, we became aware of a parallel study of H+/Cl− ion symport using a different set of prodigiosin analogues, namely a set of wholly synthetic pyrrole amides. See: P. A. Gale, M. E. Light, B. McNally, K. Navakhun, K. E. Sliwinski, B. D. Smith, Chem. Commun. 2005, 3773–3775. We thank the authors for making their manuscript available to us prior to publication.
- 12Experimental details and characterization data are included in the Supporting Information. CCDC 271587 and 271586 (4⋅HCl and 7⋅HCl, respectively) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
- 13A. Koulov, T. N. Lambert, R. Shukla, M. Jain, M. Boon, B. D. Smith, H. Li, D. N. Sheppard, J.-B. Joos, J. P. Clare, A. P. Davis, Angew. Chem. 2003, 115, 5081–5083;
10.1002/ange.200351957 Google ScholarAngew. Chem. Int. Ed. 2003, 42, 4931–4933; .
- 14
- 14aF. Nicol, S. Nir, F. C. Szoka, Jr., Biophys. J. 2000, 78, 818–829;
- 14bJ. P. Koniarek, J. L. Thomas, M. Vazquez, Adv. Space Res. 2004, 34, 1373–1377;
- 14cM. Castaing, A. Loiseau, L. Djoudi, Eur. J. Pharm. Sci. 2003, 18, 81–88;
- 14dA. G Krishna, S. T. Menon, T. J. Terry, T. P. Sakmar, Biochemistry 2002, 41, 8298–8309.
- 15K. Kano, J. H. Fendler, Biochim. Biophys. Acta 1978, 509, 289–299.
- 16T. Mosmann, J. Immunol. Methods 1983, 65, 55–63.
- 17A. Treibs, M. Strell, I. Strell, D. Grimn, Justus Liebigs Ann. Chem. 1978, 289–305.
- 18A. Fürstner, J. Grabowski, C. W. Lehmann, J. Org. Chem. 1999, 64, 8275–8280.
