Diamine and aminoalcohol derivatives active against Trypanosoma brucei

被引：10

作者：

del Olmo, Esther ^{[1
]}

Diaz-Gonzalez, Rosario ^{[2
]}

Escarcena, Ricardo ^{[1
]}

Carvalho, Luis ^{[2
]}

Bustos, Luis A. ^{[1
]}

Navarro, Miguel ^{[2
]}

San Feliciano, Arturo ^{[1
]}

机构：

[1] Univ Salamanca, Fac Farm, Dept Quim Farmaceut, CIETUS, E-37007 Salamanca, Spain

[2] CSIC, Inst Parasitol & Biomed Lopez Neyra, E-18100 Granada, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 01期

关键词：

Diamines; Aminoalcohols; Trypanocide; Sleeping sickness; HUMAN AFRICAN TRYPANOSOMIASIS;

D O I：

10.1016/j.bmcl.2011.10.108

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Twenty compounds selected as representative members of three series of long-chain 1,2-diamines, 2-amino-1-alkanols and 1-amino-2-alkanols structurally related to dihydrosphingosin, were synthesized and tested in vitro for their ability to inhibit the sleeping sickness parasites Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC50 values in the submicromolar range, with selectivity indexes up to 39 related to the respective cytotoxicity values for Vero cells. The parasite phenotype detected after treatment with the most potent compounds showed irreversible cell morphology alterations of the flagellar pocket that lead to inhibition of cell growth and parasite death. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：440 / 443

页数：4

共 15 条

[1] Clathrin-mediated endocytosis is essential in Trypanosoma brucei [J].

Allen, CL ;

Goulding, D ;

Field, MC .

EMBO JOURNAL, 2003, 22 (19) :4991-5002

[2] Structure-Activity Study of Pentamidine Analogues as Antiprotozoal Agents [J].

Bakunova, Svetlana M. ;

Bakunov, Stanislav A. ;

Patrick, Donald A. ;

Kumar, E. V. K. Suresh ;

Ohemeng, Kwasi A. ;

Bridges, Arlene S. ;

Wenzler, Tanja ;

Barszcz, Todd ;

Jones, Susan Kilgore ;

Werbovetz, Karl A. ;

Brun, Reto ;

Tidwell, Richard R. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (07) :2016-2035

[3] Human African trypanosomiasis: pharmacological re-engagement with a neglected disease [J].

Barrett, M. P. ;

Boykin, D. W. ;

Brun, R. ;

Tidwell, R. R. .

BRITISH JOURNAL OF PHARMACOLOGY, 2007, 152 (08) :1155-1171

[4] MOLECULAR AND CYTOTOXIC EFFECTS OF CAMPTOTHECIN, A TOPOISOMERASE-I INHIBITOR, ON TRYPANOSOMES AND LEISHMANIA [J].

BODLEY, AL ;

SHAPIRO, TA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) :3726-3730

[5] Chemotherapy against human African trypanosomiasis: Is there a road to success? [J].

Burri, Christian .

PARASITOLOGY, 2010, 137 (14) :1987-1994

[6] Leishmanicidal activity of some aliphatic diamines and amino-alcohols [J].

del Olmo, E ;

Alves, M ;

López, JL ;

Inchaustti, A ;

Yaluff, G ;

de Arias, AR ;

Feliciano, AS .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (04) :659-662

[7] Synthesis and evaluation of some lipidic aminoalcohols and diamines as immunomodulators [J].

del Olmo, Esther ;

Plaza, Alvaro ;

Muro, Antonio ;

Martinez-Fernandez, Antonio R. ;

Nogal-Ruiz, Juan J. ;

Lopez-Perez, Jose L. ;

San Feliciano, Arturo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (23) :6091-6095

[8] Simple dihydrosphyngosine analogues with potent activity against MDR-Mycobacterium tuberculosis [J].

del Olmo, Esther ;

Maria Molina-Salinas, Gloria ;

Escarcena, Ricardo ;

Alves, Mario ;

Lopez-Perez, Jose L. ;

Hernandez-Pando, Rogelio ;

Said-Fernandez, Salvador ;

San Feliciano, Arturo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (19) :5764-5768

[9] The trypanosome flagellar pocket [J].

Field, Mark C. ;

Carrington, Mark .

NATURE REVIEWS MICROBIOLOGY, 2009, 7 (11) :775-786

[10] Synthesis and enzyme inhibitory activities of a series of lipidic diamine and aminoalcohol derivatives on cytosolic and secretory phospholipases A2 [J].

Lucas, R ;

Ubeda, A ;

Payá, M ;

Alves, M ;

del Olmo, E ;

López, JL ;

San Feliciano, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (03) :285-288

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