Activities of Trimethoprim against Infections with Pyrimethamine Susceptible and Resistant Strains of Plasmodium cynomolgi

Schmidt, L. H.; Harrison, Janet; Ellison, R; P, Worcester

doi:10.3181/00379727-131-33861

Cited by 6 publications

(2 citation statements)

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“…1.1 4-9 (-) [3][4][5][6][7][8] (-) 1 14.2 (-) 14.6 (-) 1 5.7 (-) 4.9 ( ) 0.9 5.9 (-) 7.5 0 The activity was determined by the Rane Laboratory, University of Miami. Mice are given a standard inoculum of a blood-induced P. berghei infection and are treated with a single subcutaneous dose of compound suspended in peanut oil.6'7 The lowest dose which effects an increase of 100% in mean survival time is considered the minimum active dose.…”

Section: Resultsmentioning

confidence: 99%

Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli

Genther¹,

Smith²

1977

J. Med. Chem.

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As part of the search for new antimalarial drugs, a screening program was developed using sensitive and chlorguanide triazine (CGT, cycloguanil) resistant strains of the folate-requiring bacteria, Streptococcus faecium durans, Lactobacillus casei, and Pediococcus cerevisiae. The activities of 40 compounds have been studied against these strains and Escherichia coli. Observations have been made on the points of 50% growth inhibition, the fold increase of resistance shown to each compound by the resistant strains as compared with the parent sensitive strains, and the reversal of growth inhibition by folic acid with S. faecium and L. casei by folinic acid with P. cerevisiae and by p-aminobenzoic acid with E. coli. Comparisons have been made of the activities of the test compounds with those of the standard antimalarial antifoltes, CGT and pyrimethamine (PM), and the antibacterial results have been compared with the activities of the compounds against Plasmodium berghei infections in the mouse and against human malaria infections where data are available. Of the 17 compounds reversed by folates, five had patterns of activity similar to CGT and PM in that they were most active against S. faecium and nine compounds exhibited a different pattern, being highly active against all four test bacteria. This suggests that these latter compounds either have different pharmacokinetic properties or have additional modes of action. The three CGT-resistant organisms responded to antifolates in different ways. S. faecium (R) and P. cerevisiae (R) strains were cross resistant to 4,6-diaminotriazines, 2,4-diaminopyrimidines, 2,4-diaminoquinazolines, and active 2,4-diaminopteridines. L. casei (R) was cross resistant to the triazines but was collaterally sensitive to all the other antifolates. Most of the compounds not reversed by folates were much less inhibitory for the test organisms; they were most active against L. casei. In general, their growth inhibitory concentrations varied less for the four test organisms and the responses of the sensitive and CGTR strains were similar. However, there was some cross resistance to five compounds and some collateral sensitivity to five others. Comparison of the bacteriological data with the activities of the compounds against Plasmodium berghei in the mouse showed little correlation between the two test systems; each appears to provide independent and useful information.

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Section: Resultsmentioning

confidence: 99%

Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli

Genther¹,

Smith²

1977

J. Med. Chem.

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“…Furthermore, because of the general structural similarities of these compounds, cross-resistance to other antifolates has been a frequent but not invariable finding both in malarial parasites (1, 13,14,16) and in bacteria (9,17). The conclusion has been drawn that resistance to this type of compound is due to a multiplicity of mechanisms (8,9).…”

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confidence: 91%

Cross-Resistance and Collateral Susceptibility to Antifolic Antimalarial Compounds

Smith

Genther

1972

Antimicrob Agents Chemother

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Series of strains of Streptococcus faecium ATCC 8043, Lactobacillus casei ATCC 7469, and Pediococcus cerevisiae ATCC 8081 with increasing resistance to the active antifolate antimalarial drugs chlorguanide triazine (CGT), pyrimethamine (PM), and trimethoprim (TMP) were isolated. These mutant strains, stable for at least 3 to 5 years, were examined for cross-resistance and collateral susceptibility to the above compounds and to methotrexate (MTX). Generally, they exhibited crossresistance to all four compounds, but resistance of a strain to one compound did not predict accurately its resistance to another drug. Unexpectedly, L. casei resistant to CGT exhibited collateral susceptibility to MTX, TMP, and PM varying from 5-to 20-fold. P. cerevisiae developed resistance to CGT readily but maintained its susceptibility to PM and TMP after prolonged exposure to these compounds. Resistance to these antimalarial antifolates was accompanied by only lowgrade cross-resistance to MTX, a representative antileukemic antifolate agent.

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Malaria Models in Simian Hosts

Rossan¹

1984

Handbook of Experimental Pharmacology

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Activities of Trimethoprim against Infections with Pyrimethamine Susceptible and Resistant Strains of Plasmodium cynomolgi

Cited by 6 publications

References 0 publications

Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli

Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli

Cross-Resistance and Collateral Susceptibility to Antifolic Antimalarial Compounds

Malaria Models in Simian Hosts

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