In vitro susceptibility of Acanthamoeba culbertsoni to inhibitors of folate biosynthesis.
The effects of different sulphonamides, dihydrofolate reductase inhibitors and other inhibitors of folate metabolism on growth of Acanthamoeba culbertsoni in a chemically defined medium are reported. Among the sulphonamides, sulphamethoxazole and sulphadiazine were most effective followed by sulphanilamide and sulphaguanidine. Inhibition by each sulphonamide was reversed by p-aminobenzoic acid as well as folic acid. 7-Methylguanosine, a pteridine synthesis-inhibitor, did not inhibit multiplication of A. culbertsoni. Among the dihydrofolate reductase inhibitors, pyrimethamine blocked the amoebic growth at 100 micrograms/ml, while trimethoprim and cycloguanil palmoate failed to cause significant inhibition of growth even at 250 micrograms/ml. Metoprine inhibited amoebic growth completely at 50 micrograms/ml. Methotrexate and a thymidylate synthetase inhibitor 5-fluorouracil inhibited growth strongly, with IC50 values (the concentration of the drug which causes 50% inhibition of the growth at 72 h) of 1.97 and 2.45 micrograms/ml, respectively. Inhibition by methotrexate, metoprine or 5-fluorouracil could not be reversed by folic acid, folinic acid, thymidine, or folinic acid plus thymidine. The results indicate unusual features in A. culbertsoni folate metabolism.
Mehlotra
R K
RK
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Shukla
O P
OP
D000048:Acanthamoeba / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D003470:Culture Media; D005492:Folic Acid / Q000096:biosynthesis*; D005493:Folic Acid Antagonists; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D003470:Culture Media; D005493:Folic Acid Antagonists; D013449:Sulfonamides; D006151:Guanosine; C016578:7-methylguanosine; D005492:Folic Acid; D013940:Thymidylate Synthase