Synthesis and structure-activity relationship of disubstituted benzamides as a novel class of antimalarial agents

被引：14

作者：

Mitachi, Katsuhiko ^{[1
]}

Salinas, Yandira G. ^{[1
]}

Connelly, Michele ^{[1
]}

Jensen, Nicholas ^{[1
]}

Ling, Taotao ^{[1
]}

Rivas, Fatima ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 14期

关键词：

Plasmodium falciparum; Disubstituted benzamides; Antimalarial agents; MALARIA;

D O I：

10.1016/j.bmcl.2012.05.124

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Malaria is a devastating world health problem. Using a compound library screening approach, we identified a novel series of disubstituted benzamide compounds with significant activity against malaria strains 3D7 and K1. These compounds represent a new antimalarial molecular scaffold exemplified by compound 1, which demonstrated EC50 values of 60 and 430 nM against strains 3D7 and K1, respectively. Herein we report our findings on the efficient synthesis, structure-activity relationships, and biological activity of this new class of antimalarial agents. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4536 / 4539

页数：4

共 15 条

[1] Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease [J].

Bolognesi, Maria Laura ;

Banzi, Rita ;

Bartolini, Manuela ;

Cavalli, Andrea ;

Tarozzi, Andrea ;

Andrisano, Vincenza ;

Minarini, Anna ;

Rosini, Michela ;

Tumiatti, Vincenzo ;

Bergamini, Christian ;

Fato, Romana ;

Lenaz, Giorgio ;

Hrelia, Patrizia ;

Cattaneo, Antonino ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (20) :4882-4897

[2] Chloroquine resistance reversal agents as promising antimalarial drugs [J].

Henry, Maud ;

Alibert, Sandrine ;

Orlandi-Pradines, Eve ;

Bogreau, Herve ;

Fusai, Thierry ;

Rogier, Christophe ;

Barbe, Jacques ;

Pradines, Bruno .

CURRENT DRUG TARGETS, 2006, 7 (08) :935-948

[3] That Was Then But This Is Now: Malaria Research in the Time of an Eradication Agenda [J].

Kappe, Stefan H. I. ;

Vaughan, Ashley M. ;

Boddey, Justin A. ;

Cowman, Alan F. .

SCIENCE, 2010, 328 (5980) :862-866

[4] Synthesis and in vitro protozoocidal activity of diazabicyclic benzotropolone derivatives [J].

Khrizman, Alexander ;

Moulthrop, Jason S. ;

Little, Susan ;

Wharton, Hayley ;

Yardley, Vanessa ;

Moyna, Guillermo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (15) :4183-4186

[5] A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance [J].

Lakshmanan, V ;

Bray, PG ;

Verdier-Pinard, D ;

Johnson, DJ ;

Horrocks, P ;

Muhle, RA ;

Alakpa, GE ;

Hughes, RH ;

Ward, SA ;

Krogstad, DJ ;

Sidhu, ABS ;

Fidock, DA .

EMBO JOURNAL, 2005, 24 (13) :2294-2305

[6]

Lueze E. I., 1996, J ANTIMICROB CHEMOTH, V37, P511

[7] Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities [J].

Madrid, PB ;

Sherrill, J ;

Liou, AP ;

Weisman, JL ;

DeRisi, JL ;

Guy, RK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (04) :1015-1018

[8] Antimalarial activity of thiosemicarbazones and purine derived nitriles [J].

Mallari, Jeremy P. ;

Guiguemde, Wendyam A. ;

Guy, R. Kiplin .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (13) :3546-3549

[9] Chloroquine Transport via the Malaria Parasite's Chloroquine Resistance Transporter [J].

Martin, Rowena E. ;

Marchetti, Rosa V. ;

Cowan, Anna I. ;

Howitt, Susan M. ;

Broeer, Stefan ;

Kirk, Kiaran .

SCIENCE, 2009, 325 (5948) :1680-1682

[10] Antimalarial drugs - What is in use and what is in the pipeline [J].

Schlitzer, Martin .

ARCHIV DER PHARMAZIE, 2008, 341 (03) :149-163

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