Synthesis, electrochemistry, and bioactivity of the cyanobacterial calothrixins and related quinones

Paul H. Bernardo; Christina L.L. Chai; Graham A. Heath; Peter J. Mahon; Geoffrey D. Smith; Paul Waring; Bronwyn A. Wilkes

doi:10.1021/jm049625o

Synthesis, electrochemistry, and bioactivity of the cyanobacterial calothrixins and related quinones

Paul H. Bernardo, Christina L.L. Chai, Graham A. Heath, Peter J. Mahon, Geoffrey D. Smith, Paul Waring, Bronwyn A. Wilkes

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

111 Citations (Scopus)

Abstract

The calothrixins are quinone-based natural products isolated from Calothrix cyanobacteria which show potent antiproliferative properties against several cancer cell lines. Preliminary mechanistic studies suggest that the biological mode of action of the calothrixins maybe linked to their ability to undergo redox cycling. In this study we compare the bioactivities of the calothrixins with those of structurally related quinones in order to identify the structural features in the calothrixins essential for biological activity. In particular, the reduction potentials of the calothrixins and some related quinones were measured electrochemically. Our studies indicate that while there is no direct correlation between the reduction potentials and biological activities of the studied compounds, in all cases quinones with EC₅₀ values <1.6 μM undergo reduction to their respective semiquinones readily, with their E_1/2 values being more positive than -0.5 V versus the standard hydrogen electrode (SHE).

Original language	English
Pages (from-to)	4958-4963
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	47
Issue number	20
DOIs	https://doi.org/10.1021/jm049625o
Publication status	Published - 23 Sept 2004

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abstract = "The calothrixins are quinone-based natural products isolated from Calothrix cyanobacteria which show potent antiproliferative properties against several cancer cell lines. Preliminary mechanistic studies suggest that the biological mode of action of the calothrixins maybe linked to their ability to undergo redox cycling. In this study we compare the bioactivities of the calothrixins with those of structurally related quinones in order to identify the structural features in the calothrixins essential for biological activity. In particular, the reduction potentials of the calothrixins and some related quinones were measured electrochemically. Our studies indicate that while there is no direct correlation between the reduction potentials and biological activities of the studied compounds, in all cases quinones with EC50 values <1.6 μM undergo reduction to their respective semiquinones readily, with their E1/2 values being more positive than -0.5 V versus the standard hydrogen electrode (SHE).",

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AU - Bernardo, Paul H.

AU - Chai, Christina L.L.

AU - Heath, Graham A.

AU - Mahon, Peter J.

AU - Smith, Geoffrey D.

AU - Waring, Paul

AU - Wilkes, Bronwyn A.

PY - 2004/9/23

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AB - The calothrixins are quinone-based natural products isolated from Calothrix cyanobacteria which show potent antiproliferative properties against several cancer cell lines. Preliminary mechanistic studies suggest that the biological mode of action of the calothrixins maybe linked to their ability to undergo redox cycling. In this study we compare the bioactivities of the calothrixins with those of structurally related quinones in order to identify the structural features in the calothrixins essential for biological activity. In particular, the reduction potentials of the calothrixins and some related quinones were measured electrochemically. Our studies indicate that while there is no direct correlation between the reduction potentials and biological activities of the studied compounds, in all cases quinones with EC50 values <1.6 μM undergo reduction to their respective semiquinones readily, with their E1/2 values being more positive than -0.5 V versus the standard hydrogen electrode (SHE).

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Synthesis, electrochemistry, and bioactivity of the cyanobacterial calothrixins and related quinones

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