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Inhibition by pyrimidine analogues of the synthesis of folic acid by trachoma agents

Published online by Cambridge University Press:  15 May 2009

P. Reeve ,
Janice Taverne  and
S. R. M. Bushby
P. Reeve
Affiliation:
M.R.C. Trachoma Research Unit, Lister Institute of Preventive Medicine, London, S. W. 1
Janice Taverne
Affiliation:
M.R.C. Trachoma Research Unit, Lister Institute of Preventive Medicine, London, S. W. 1
S. R. M. Bushby
Affiliation:
Wellcome Research Laboratories, Beckenham, Kent
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Trimethoprim, a 2,4-diaminopyrimidine derivative which inhibits the growth of some bacteria by interfering with folic acid synthesis, inhibited the growth of several strains of the trachoma agent. Inhibition was most clearly demonstrated by measuring prolongation of mean death time of groups of chick embryos inoculated with a single lethal dose of agent. Over a certain range, prolongation was proportional to the logarithm of concentration of inhibitor; higher concentrations were toxic for the embryo. On a weight basis, trimethoprim was not as active as sulphafurazole. Inoculation in conjunction with sulphafurazole resulted in slight potentiation of activity. A related pyrimidine derivative, the antimalarial drug pyrimethamine, also significantly inhibited the growth of one strain of trachoma.

In cell culture, trimethoprim decreased the number of inclusions formed by a suspension of the trachoma agent and induced morphological changes in the inclusions similar to those caused by sulphafurazole.

Inhibition of the growth of the trachoma agent in the chick embryo was reversed by leucovorin calcium. It is concluded that, as with bacteria, the drug acts by blocking the folio acid cycle and that the trachoma agent most probably contains a dihydrofolate reductase.

Type
Original Articles
Information
Journal of Hygiene , Volume 66 , Issue 2 , June 1968 , pp. 295 - 306
Copyright
Copyright © Cambridge University Press 1968

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