In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

Sarah Schleiferbock; Christian Scheurer; Masataka Ihara; Isamu Itoh; Ian C Bathurst; Jeremy Burrows; Pascal Fantauzzi; Julie Lotharius; Susan Ann Charman; Julia Morizzi; David Shackleford; Karen Louise White; Reto Brun; Sergio Wittlin

doi:10.2147/DDDT.S51298

In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

Sarah Schleiferbock, Christian Scheurer, Masataka Ihara, Isamu Itoh, Ian C Bathurst, Jeremy Burrows, Pascal Fantauzzi, Julie Lotharius, Susan Ann Charman, Julia Morizzi, David Shackleford, Karen Louise White, Reto Brun, Sergio Wittlin

Centre for Drug Candidate Optimisation

Research output: Contribution to journal › Article › Research › peer-review

12 Citations (Scopus)

Abstract

The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.

Original language	English
Pages (from-to)	1377 - 1384
Number of pages	8
Journal	Drug Design, Development and Therapy
Volume	7
DOIs	https://doi.org/10.2147/DDDT.S51298
Publication status	Published - 2013

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Schleiferbock, S., Scheurer, C., Ihara, M., Itoh, I., Bathurst, I. C., Burrows, J., Fantauzzi, P., Lotharius, J., Charman, S. A., Morizzi, J., Shackleford, D., White, K. L., Brun, R., & Wittlin, S. (2013). In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models. Drug Design, Development and Therapy, 7, 1377 - 1384. https://doi.org/10.2147/DDDT.S51298

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title = "In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models",

abstract = "The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.",

author = "Sarah Schleiferbock and Christian Scheurer and Masataka Ihara and Isamu Itoh and Bathurst, {Ian C} and Jeremy Burrows and Pascal Fantauzzi and Julie Lotharius and Charman, {Susan Ann} and Julia Morizzi and David Shackleford and White, {Karen Louise} and Reto Brun and Sergio Wittlin",

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doi = "10.2147/DDDT.S51298",

language = "English",

volume = "7",

pages = "1377 -- 1384",

journal = "Drug Design, Development and Therapy",

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Schleiferbock, S, Scheurer, C, Ihara, M, Itoh, I, Bathurst, IC, Burrows, J, Fantauzzi, P, Lotharius, J, Charman, SA, Morizzi, J, Shackleford, D, White, KL, Brun, R & Wittlin, S 2013, 'In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models', Drug Design, Development and Therapy, vol. 7, pp. 1377 - 1384. https://doi.org/10.2147/DDDT.S51298

TY - JOUR

T1 - In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

AU - Schleiferbock, Sarah

AU - Scheurer, Christian

AU - Ihara, Masataka

AU - Itoh, Isamu

AU - Bathurst, Ian C

AU - Burrows, Jeremy

AU - Fantauzzi, Pascal

AU - Lotharius, Julie

AU - Charman, Susan Ann

AU - Morizzi, Julia

AU - Shackleford, David

AU - White, Karen Louise

AU - Brun, Reto

AU - Wittlin, Sergio

PY - 2013

Y1 - 2013

N2 - The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.

AB - The objective of this work was to characterize the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832383/pdf/dddt-7-1377.pdf

U2 - 10.2147/DDDT.S51298

DO - 10.2147/DDDT.S51298

M3 - Article

SN - 1177-8881

VL - 7

SP - 1377

EP - 1384

JO - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

ER -

In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

Abstract

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