Achiral, cheap, and potent inhibitors of plasmepsins I, II, and IV

被引：47

作者：

Boss, Christoph

Corminboeuf, Olivier

Grisostomi, Corinna

Meyer, Solange

Jones, Andrew F.

Prade, Lars

Binkert, Christoph

Fischli, Walter

Weller, Thomas

Bur, Daniel

机构：

[1] Drug Discovery, Chemistry and Biology, Actelion Pharmaceuticals Ltd., 4123 Allschwil

来源：

CHEMMEDCHEM | 2006年 / 1卷 / 12期

关键词：

Aspartic proteases; Drug design; Inhibitors; Malaria; Medicinal chemistry;

D O I：

10.1002/cmdc.200600223

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of molecules targeting aspartic proteinases from P falciparum is described. Synthesis of these easily available, achiral, and highly potent molecules was supported by structural information and eventually allowed the identification of compounds highly active against three vacuolar aspartic proteinases. In a red blood cell assay, the growth of P. falciparurn (strain K1) could be effectively prevented.

引用

页码：1341 / +

页数：6

共 26 条

[1] The Cambridge Structural Database: a quarter of a million crystal structures and rising [J].

Allen, FH .

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 2002, 58 (3 PART 1) :380-388

[2] Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine [J].

Banerjee, R ;

Liu, J ;

Beatty, W ;

Pelosof, L ;

Klemba, M ;

Goldberg, DE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (02) :990-995

[3] Structural insights into the activation of P-vivax plasmepsin [J].

Bernstein, NK ;

Cherney, MM ;

Yowell, CA ;

Dame, JB ;

James, MNG .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 329 (03) :505-524

[4] A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum [J].

Berry, C ;

Humphreys, MJ ;

Matharu, P ;

Granger, R ;

Horrocks, P ;

Moon, RP ;

Certa, U ;

Ridley, RG ;

Bur, D ;

Kay, J .

FEBS LETTERS, 1999, 447 (2-3) :149-154

[5] Replacement of isobutyl by trifluoromethyl in pepstatin A selectively affects inhibition of aspartic proteinases [J].

Binkert, C ;

Frigerio, M ;

Jones, A ;

Meyer, S ;

Pesenti, C ;

Prade, L ;

Viani, F ;

Zanda, M .

CHEMBIOCHEM, 2006, 7 (01) :181-186

[6] Inhibitors of aspartic proteases - potential antimalarial agents [J].

Boss, C ;

Corminboeuf, O ;

Grisostomi, C ;

Weller, T .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2006, 16 (03) :295-317

[7] Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents [J].

Boss, C ;

Richard-Bildstein, S ;

Weller, T ;

Fischli, W ;

Meyer, S ;

Binkert, C .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (11) :883-907

[8] Structure of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae bound to an allophenylnorstatine-based inhibitor [J].

Clemente, JC ;

Govindasamy, L ;

Madabushi, A ;

Fisher, SZ ;

Moose, RE ;

Yowell, CA ;

Hidaka, K ;

Kimura, T ;

Hayashi, Y ;

Kiso, Y ;

Agbandje-McKenna, M ;

Dame, JB ;

Dunn, BM ;

McKenna, R .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2006, 62 :246-252

[9] Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets [J].

Coombs, GH ;

Goldberg, DE ;

Klemba, M ;

Berry, C ;

Kay, J ;

Mottram, JC .

TRENDS IN PARASITOLOGY, 2001, 17 (11) :532-537

[10] Genome sequence of the human malaria parasite Plasmodium falciparum [J].

Gardner, MJ ;

Hall, N ;

Fung, E ;

White, O ;

Berriman, M ;

Hyman, RW ;

Carlton, JM ;

Pain, A ;

Nelson, KE ;

Bowman, S ;

Paulsen, IT ;

James, K ;

Eisen, JA ;

Rutherford, K ;

Salzberg, SL ;

Craig, A ;

Kyes, S ;

Chan, MS ;

Nene, V ;

Shallom, SJ ;

Suh, B ;

Peterson, J ;

Angiuoli, S ;

Pertea, M ;

Allen, J ;

Selengut, J ;

Haft, D ;

Mather, MW ;

Vaidya, AB ;

Martin, DMA ;

Fairlamb, AH ;

Fraunholz, MJ ;

Roos, DS ;

Ralph, SA ;

McFadden, GI ;

Cummings, LM ;

Subramanian, GM ;

Mungall, C ;

Venter, JC ;

Carucci, DJ ;

Hoffman, SL ;

Newbold, C ;

Davis, RW ;

Fraser, CM ;

Barrell, B .

NATURE, 2002, 419 (6906) :498-511

← 1 2 3 →