On the antifungal mode of action of metalaxyl, an inhibitor of nucleic acid synthesis in Pythium splendens

Chemicals/CAS: metalaxyl, 57837-19-1; mithramycin, 18378-89-

On a difference in the antifungal activity of tridemorph and its formulated product Calixin

The antifungal effects of tridemorph and its formulated product Calixin were compared in vitro on Ustilago maydis, Saccharomyces cerevisiae, Torulopsis candida, Botrytis allii, and Cladosporium cucumerinum. MIC values for both products were about the same. In liquid media the products were somewhat more effective than on solid media. T. candida proved sensitive only at pH 5, but the other organisms were as sensitive at pH 7 as at pH 5. Whereas tridemorph even at high concentrations did not affect oxygen consumption of these organisms, Calixin at concentrations slightly above the MIC values appeared to inhibit respiration. This effect of Calixin could be explained by the presence of Nekanil LN in the formulation. This compound inhibited both growth and respiration of the organisms at high concentrations; however, in the simultaneous presence of tridemorph a synergistic effect on oxygen consumption was observed

On the mode of action of 3 phenylindole towards Aspergillus niger

3 Phenylindole is an antimicrobial compound active towards many fungi and gram positive bacteria. At 5 μg/ml it inhibits growth of Aspergillus niger. Higher concentrations (50 μg/ml) also suppress spore germination; they do not kill the fungus. Dry weight of the fungus still increases for 1 or 2 days after fungicide treatment. The toxicant has no effect on O2 uptake even at higher concentrations (100 μg/ml). The compound markedly affects composition of the lipid fraction of A. niger inducing a decrease in phospholipid concentration with a coincident increase in free fatty acids. Sterol pattern and sterol concentrations were not affected. Antifungal activity was reversed by phospholipids added to the medium. 3 Phenylindole induced a slight leakage of 32P labeled compounds from the treated cells under growth conditions but not under nongrowth conditions. A strain of A. niger resistant to 3 phenylindole had the same phospholipid and sterol pattern as the wild type, but the level of both components was higher (40-60%). The 3 phenylindole resistant strain showed resistance to triarimol and pimaricin. The wild type and the resistant strain both took up 3 phenylindole quite rapidly and accumulated it in the mycelium. 3 Phenylindole possibly interferes with phospholipid function in cell membranes, although the specific site of action has not yet been elucidated. Chemicals/CAS: ergosterol, 23637-22-1, 2418-45-3, 3992-98-1, 57-87-

On the antifungal mode of action of tridemorph

Tridemorph (2,6-dimethyl-N-tridecylmorpholine) was active against representative of nearly all taxonomic groups of fungi; gram-positive bacteria were also sensitive although gram-negative were not. Tridemorph, 3–10 μg/ml, inhibited the multiplication of sporidia of Ustilago maydis more strongly than the increase of dry weight. The treated sporidia appeared swollen, multicellular, and sometimes branched. Unsaturated lipophilic compounds like α-tocopherol and trilinolein alleviated the toxicity of tridemorph to Botrytis allii and U. maydis. Protein and RNA syntheses were inhibited slightly. DNA synthesis was rather strongly affected already after 2 hr. Lipid synthesis was first inhibited but later stimulated. At an early stage (2 hr) treated cells differed already from control cells by a higher content of free fatty acids. Tridemorph also inhibited sterol biosynthesis. The antimicrobial spectrum, the characteristic morphology of treated cells of U. maydis, the observations on cross-resistance, the alleviating effect of unsaturated lipophilic compounds, and the alterations in neutral lipid pattern suggest strong similarity of the mode of action of tridemorph with that of the known inhibitors of sterol biosynthesis