Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity

被引：66
作者：
Ohkanda, J
Lockman, JW
Yokoyama, K
Gelb, MH
Croft, SL
Kendrick, H
Harrell, MI
Feagin, JE
Blaskovich, MA
Sebti, SM
Hamilton, AD
机构：
[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA
[2] Univ Washington, Dept Chem, Seattle, WA 98195 USA
[3] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[4] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
[5] Seattle Biomed Res Inst, Seattle, WA 98109 USA
[6] Univ Washington, Sch Publ Hlth & Community Med, Dept Pathobiol, Seattle, WA 98195 USA
[7] Univ S Florida, Dept Biochem & Mol Biol, H Lee Moffit Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 06期
关键词：
D O I：
10.1016/S0960-894X(01)00055-5
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Malaria continues to represent a very serious health problem in the tropics. The current methods of clinical treatment are showing deficiencies due to the increased incidence of resistance in the parasite. In the present paper we report the design, synthesis, and evaluation of potential antimalarial agents against a novel target, protein farnesyltransferase. We show that the most potent compounds are active against Plasmodium falciparum in vitro at submicromolar concentrations. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：761 / 764
页数：4
相关论文
共 16 条
[1]  
BUCKNER F, 2000, IN PRESS J BIOL CHEM
[2]  
CHAKARABARTI D, 1998, MOL BIOCHEM PARASIT, P175
[3]   QUANTITATIVE ASSESSMENT OF ANTI-MALARIAL ACTIVITY INVITRO BY A SEMIAUTOMATED MICRODILUTION TECHNIQUE [J].
DESJARDINS, RE ;
CANFIELD, CJ ;
HAYNES, JD ;
CHULAY, JD .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1979, 16 (06) :710-718
[4]   Characterization of native falcipain, an enzyme involved in Plasmodium falciparum hemoglobin degradation [J].
Francis, SE ;
Gluzman, IY ;
Oksman, A ;
Banerjee, D ;
Goldberg, DE .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1996, 83 (02) :189-200
[5]   Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].
Jomaa, H ;
Wiesner, J ;
Sanderbrand, S ;
Altincicek, B ;
Weidemeyer, C ;
Hintz, M ;
Türbachova, I ;
Eberl, M ;
Zeidler, J ;
Lichtenthaler, HK ;
Soldati, D ;
Beck, E .
SCIENCE, 1999, 285 (5433) :1573-1576
[6]   An overview of chemotherapeutic targets for antimalarial drug discovery [J].
Olliaro, PL ;
Yuthavong, Y .
PHARMACOLOGY & THERAPEUTICS, 1999, 81 (02) :91-110
[7]   Probing the hydrophobic pocket of farnesyltransferase: Aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors [J].
Qian, YM ;
Marugan, JJ ;
Fossum, RD ;
Vogt, A ;
Sebti, SM ;
Hamilton, AD .
BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (12) :3011-3024
[8]   Design and synthesis of non-peptide Ras CAAX mimetics as potent farnesyltransferase inhibitors [J].
Qian, YM ;
Vogt, A ;
Sebti, SM ;
Hamilton, AD .
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (01) :217-223
[9]   Proteases of malaria parasites: New targets for chemotherapy [J].
Rosenthal, PJ .
EMERGING INFECTIOUS DISEASES, 1998, 4 (01) :49-57
[10]  
SEBTI SM, 1997, PHARMACOL THERAPEUT, V71, P1
12