Fungistatic Activity of Propyl-N-(γ-dimethylaminopropyl) carbamate on Pythium spp. and its Reversal by Sterols

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Abstract
In vitro fungistatic activity of the new systemic fungicide propyl-N-(.gamma.-dimethylaminopropyl)carbamate HCl [PDAC, SN66752, propamocarb (proposed)] was studied in solid and liquid synthetic medium (BM-1 [basal medium 1]) against 8 Pythium spp. [P. aphanidermatum, P. debaryanum, P. splendens, P. myriotylum, P. irregulare, P. ultimum, P. arrhenomanes, P. butleri]. The PDAC at concentrations up to 5 .mu.g active ingredient (a.i.)/ml was less fungistatic to Pythium spp. than was its S-analog, N-(3-dimethylaminopropyl) thiocarbamic acid Shylester HCl [DTEH, SN41703, prothiocarb (proposed)]. The dosage-response curves for PDAC were linear from 0.5 to 10 .mu.g a.i./ml, with ED50 values ranging 2.5-5 .mu.g/ml for all species except P. myriotylum which had an ED50 value of about 0.1 .mu.g a.i./ml or less. Four Pythium spp. (not including P. myriotylum) were more sensitive to PDAC at pH of 7.4 than at 6.4 or 5.3. Cholesterol added to BM-1 at 5-30 .mu.g/ml reversed the fungistatic activity of PDAC, but the magnitude of reversal depended on PDAC concentration in BM-1 and on the Pythium sp. used. Cholestanol and sitosterol, but not lanosterol, also reversed activity. With P. myriotylum, even 30 .mu.g/ml of cholesterol did not reverse activity. Greater amounts of cellular constituents (proteins, carbohydrates, amino acids and soluble salts) leaked from mycelia of Pythium grown in liquid BM-1 supplemented with 0.5 .mu.g a.i./ml PDAC than from mycelia grown in PDAC-free medium. In general, the rate of leakage was constant over a 7 h period for most cell constituents except soluble salts. Cholesterol added to BM-1 reduced leakage of cell constituents. When added with PDAC, cholesterol reversed the effects of the fungicide on mycelium cell membrane permeability.