Bioactive secondary metabolites of cyanobacteria
Most of our work is now concentrated on bioactive metabolites of cyanobacteria,
particularly the calothrixins, which were discovered in a Calothrix
cyanobacterium by our group. They have been shown to have strong anticancer
activity in cell culture against a number of cancer cells, including
drug-resistant ones. Their biochemical modes of action are being studied.
This is being done as a collaborative project with Drs Christina Chai
and Paul Waring in the Department of Chemistry. We are also synthesizing
a range of chemical variants of the natural products with a view to
doing structure/activity studies and producing analogues which might
have properties more suited to pharmaceutical application.
It could be noted that a new Centre for the Study of Bioactive Molecules
has been proposed for ANU, which is a collaboration between this laboratory
and members of the Department of Chemistry and Research School of Chemistry.
The centre offers interdisciplinary collaborative projects, with cyanobacteria,
fungi and lichins as the main organisms of interest.
Groundwater nitrate and public health
This is a continuing area of interest and relates to the high levels
of nitrate in the groundwaters of central Australia, derived from natural
sources, and in south-east Asia (particularly Indonesia), derived from
the nature of village sanitation. Both represent environmental health
problems and the World Health Organization has issued a guideline limit
of 50 mg L-1 in drinking water. Our work has been concerned with understanding
the origins of the nitrate, the health consequences for people drinking
the water, and possible solutions to the problem. We are also interested
in the relationship between groundwater nitrate and the incidence of
infectious disease, particularly Shigellosis, which is responsible for
millions of deaths of children in the developing world. |
Chen, X., Smith, G.D. and Waring, P. (2003) Human cancer cell (Jurkat)
killing by the cyanobacterial metabolite calothrixin A. J. Appl.
Phycol. 15, 269-277.
Doan, N.T., Stewart, P.R. and Smith, G.D. (2001) Inhibition of bacterial
RNA polymerase by the cyanobacterial metabolites 12-epi-hapalindole
E isonitrile and calothrixin A. FEMS Micrbiol. Lett., 196,
135-139.
Smith, G.D., Wetselaar, R., Fox, J.J., Hidayati, D. and Yogaswara,
H. (2000) Ingestion of well water with high nitrate concentrations by
village people in Indonesia: methaemoglobin and haemoglobin measurements. AMBIO 29, 525-527.
Doan, N.G., Rickards, R.W., Rothschild, J.M. and Smith, G.D. (2000)
Allelopathic actions of the alkaloids 12-epi-hapalindole E isonitrile
and calothrixin A from cyanobacteria of the genera Fischerella and Calothrix. J. Appl. Phycol. 12, 409-416.
Schlegel, I., Doan, N.T., de Chazal, N.M. and Smith, G.D. (1999) Antibiotic
activity of new cyanobacterial isolates from Australia and Asia against
green algae and cyanobacteria. J. Appl. Phycol. 10, 471-479.
Rickards, R.W., Rothschild, J.M., Willis, A.C., de Chazal, N.M., Kirk,
J., Kirk, K., Saliba, K.J. and Smith, G.D. (1999) Calothrixins A and
B, Novel Pentacyclic Metabolites from Calothrix Cyanobacteria with Potent
Activity against Malaria Parasites and Human Cancer Cells. Tetrahedron 55, 13513-13520.
Smith, G. D. and Doan, N.T. (1999) Cyanobacterial metabolites with
bioactivity against photosynthesis in cyanobacteria, algae and higher
plants. J. Appl. Phycol. 11, 337-344.
Barnes, C.J., Jacobson, G. and Smith, G.D. (1992) The Origin of High
Nitrate Groundwaters in the Australian Arid Zone. J. Hydrology 137, 181-197.
Smith, G.D., Wetselaar, R., Fox, J.J., van de Graaff, R.H.M., Moeljohardjo,
D., Sarwono, J., Wiranto, Asj'ari, S.R., Tjojudo, S and Basuki (1999)
The origin and distribution of nitrate in groundwater from village wells
in Kota Gede, Yogyakarta, Indonesia. Hydrogeology J. 7, 576-589.
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