Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.

Rohan A Davis; Malcolm S Buchanan; Sandra Duffy; Vicky M Avery; Susan Ann Charman; William Neil Charman; Karen Louise White; David Shackleford; Michael D Edstein; Katherine Andrews; David G Camp; Ronald J Quinn

doi:10.1021/jm3002795

Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.

Rohan A Davis, Malcolm S Buchanan, Sandra Duffy, Vicky M Avery, Susan Ann Charman, William Neil Charman, Karen Louise White, David Shackleford, Michael D Edstein, Katherine Andrews, David G Camp, Ronald J Quinn

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

39 Citations (Scopus)

Abstract

A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC 50 values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC 50 <100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC 50 = 1-4 ?M). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg -1 day -1.

Original language	English
Pages (from-to)	5851 - 5858
Number of pages	8
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	12
DOIs	https://doi.org/10.1021/jm3002795
Publication status	Published - 2012

Cite this

Davis, R. A., Buchanan, M. S., Duffy, S., Avery, V. M., Charman, S. A., Charman, W. N., ... Quinn, R. J. (2012). Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp. Journal of Medicinal Chemistry, 55(12), 5851 - 5858. https://doi.org/10.1021/jm3002795

Davis, Rohan A ; Buchanan, Malcolm S ; Duffy, Sandra ; Avery, Vicky M ; Charman, Susan Ann ; Charman, William Neil ; White, Karen Louise ; Shackleford, David ; Edstein, Michael D ; Andrews, Katherine ; Camp, David G ; Quinn, Ronald J. / Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 12. pp. 5851 - 5858.

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title = "Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.",

abstract = "A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC 50 values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC 50 <100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC 50 = 1-4 ?M). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg -1 day -1.",

author = "Davis, {Rohan A} and Buchanan, {Malcolm S} and Sandra Duffy and Avery, {Vicky M} and Charman, {Susan Ann} and Charman, {William Neil} and White, {Karen Louise} and David Shackleford and Edstein, {Michael D} and Katherine Andrews and Camp, {David G} and Quinn, {Ronald J}",

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pages = "5851 -- 5858",

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Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp. / Davis, Rohan A; Buchanan, Malcolm S; Duffy, Sandra; Avery, Vicky M; Charman, Susan Ann ; Charman, William Neil; White, Karen Louise; Shackleford, David; Edstein, Michael D; Andrews, Katherine; Camp, David G; Quinn, Ronald J.

In: Journal of Medicinal Chemistry, Vol. 55, No. 12, 2012, p. 5851 - 5858.

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

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T1 - Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.

AU - Davis, Rohan A

AU - Buchanan, Malcolm S

AU - Duffy, Sandra

AU - Avery, Vicky M

AU - Charman, Susan Ann

AU - Charman, William Neil

AU - White, Karen Louise

AU - Shackleford, David

AU - Edstein, Michael D

AU - Andrews, Katherine

AU - Camp, David G

AU - Quinn, Ronald J

PY - 2012

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N2 - A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC 50 values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC 50 <100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC 50 = 1-4 ?M). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg -1 day -1.

AB - A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC 50 values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC 50 <100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC 50 = 1-4 ?M). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg -1 day -1.

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