Synthesis, electrochemistry, and bioactivity of the cyanobacterial calothrixins and related quinones.
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 may be 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 EC(50) values <1.6 microM 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).
Bernardo
Paul H
PH
Department of Chemistry and School of Biochemistry and Molecular Biology, Centre for the Study of Bioactive Molecules, Australian National University, ACT 0200, Australia.
Chai
Christina L L
CL
Heath
Graham A
GA
Mahon
Peter J
PJ
Smith
Geoffrey D
GD
Waring
Paul
P
Wilkes
Bronwyn A
BA
D001669:Biochemical Phenomena; D001671:Biochemistry; D002470:Cell Survival / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry; D004563:Electrochemistry / Q000379:methods*; D004611:Ellipticines / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004611:Ellipticines; D026121:Indole Alkaloids; D007211:Indoles; D011809:Quinones; C418328:calothrixin A; C418327:calothrixin B