Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum

Komagal Kannan Sivaraman; Alessandro Paiardini; Marcin Sieńczyk; Chiara Ruggeri; Christine A. Oellig; John P. Dalton; Peter J. Scammells; Marcin Drag; Sheena McGowan

doi:10.1021/jm4005972

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum

Komagal Kannan Sivaraman
, Alessandro Paiardini
, Marcin Sieńczyk
, Chiara Ruggeri
, Christine A. Oellig
, John P. Dalton
, Peter J. Scammells
, Marcin Drag
, Sheena McGowan

Monash University
Sapienza University of Rome
Wroclaw University of Technology
University of Technology Sydney, Ultimo
McGill University
Cell Death and Survival Networks Program

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

59 Citations (Scopus)

Abstract

The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

Original language	English
Pages (from-to)	5213-5217
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	12
DOIs	https://doi.org/10.1021/jm4005972
Publication status	Published - 27 Jun 2013
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1021/jm4005972

Cite this

Kannan Sivaraman, K., Paiardini, A., Sieńczyk, M., Ruggeri, C., Oellig, C. A., Dalton, J. P., Scammells, P. J., Drag, M., & McGowan, S. (2013). Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum. Journal of Medicinal Chemistry, 56(12), 5213-5217. https://doi.org/10.1021/jm4005972

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title = "Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum",

abstract = "The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.",

author = "\{Kannan Sivaraman\}, Komagal and Alessandro Paiardini and Marcin Sie{\'n}czyk and Chiara Ruggeri and Oellig, \{Christine A.\} and Dalton, \{John P.\} and Scammells, \{Peter J.\} and Marcin Drag and Sheena McGowan",

year = "2013",

month = jun,

day = "27",

doi = "10.1021/jm4005972",

language = "English",

volume = "56",

pages = "5213--5217",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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}

Kannan Sivaraman, K, Paiardini, A, Sieńczyk, M, Ruggeri, C, Oellig, CA, Dalton, JP, Scammells, PJ, Drag, M & McGowan, S 2013, 'Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum', Journal of Medicinal Chemistry, vol. 56, no. 12, pp. 5213-5217. https://doi.org/10.1021/jm4005972

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum. / Kannan Sivaraman, Komagal; Paiardini, Alessandro; Sieńczyk, Marcin et al.
In: Journal of Medicinal Chemistry, Vol. 56, No. 12, 27.06.2013, p. 5213-5217.

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

TY - JOUR

T1 - Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum

AU - Kannan Sivaraman, Komagal

AU - Paiardini, Alessandro

AU - Sieńczyk, Marcin

AU - Ruggeri, Chiara

AU - Oellig, Christine A.

AU - Dalton, John P.

AU - Scammells, Peter J.

AU - Drag, Marcin

AU - McGowan, Sheena

PY - 2013/6/27

Y1 - 2013/6/27

N2 - The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

AB - The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

UR - https://www.scopus.com/pages/publications/84879558016

U2 - 10.1021/jm4005972

DO - 10.1021/jm4005972

M3 - Article

C2 - 23713488

AN - SCOPUS:84879558016

SN - 0022-2623

VL - 56

SP - 5213

EP - 5217

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 12

ER -

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum

Abstract

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