Screening of Agelasine D and Analogs for Inhibitory Activity against Pathogenic Protozoa; Identification of Hits for Visceral Leishmaniasis and Chagas Disease 英文参考文献.docVIP

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Screening of Agelasine D and Analogs for Inhibitory Activity against Pathogenic Protozoa; Identification of Hits for Visceral Leishmaniasis and Chagas Disease 英文参考文献.doc

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Screening of Agelasine D and Analogs for Inhibitory Activity against Pathogenic Protozoa; Identification of Hits for Visceral Leishmaniasis and Chagas Disease 英文参考文献

Molecules 2009, 14, 279-288; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Screening of Agelasine D and Analogs for Inhibitory Activity against Pathogenic Protozoa; Identification of Hits for Visceral Leishmaniasis and Chagas Disease Anders Vik 1, ágnes Proszenyák 1, Marieke Vermeersch 2, Paul Cos 2, Louis Maes 2,3, and Lise- Lotte Gundersen 1,* 1 Department of Chemistry, University of Oslo, P.O.Box 1033, Blindern, N-0315 Oslo, Norway; E-mails: vik.anders@ (A. V.), szenyak@kjemi.uio.no (A. P.) 2 University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Universiteitsplein 1, B-2610 Antwerp, Belgium; E-mails: marieke.vermeersch@ua.ac.be (M. V.), paul.cos@ua.ac.be (P. C.), louis.maes@ua.ac.be (L. M.) 3 Institute for Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium * Author to whom correspondence should be addressed; E-mail: l.l.gundersen@kjemi.uio.no. Received: 3 December 2008; in revised form: 29 December 2008 / Accepted: 4 January 2009/ Published: 8 January 2009 Abstract: There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC50 0.5 μg/mL) while two others displayed IC50 1 μg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research Training in Tropical Diseases