Phenylamide fungicides

Phenylamide fungicides selectively inhibit ribosomal RNA synthesis of sensitive Oomycete fungi by interference with the activity of the RNA polymerase I-template complex. 

The phenylamide fungicides, including metalaxyl and metalaxyl-M, inhibit ribo-somal RNA synthesis, specifically RNA polymerization (polymerases). In myce-... 

The phenylamide fungicides affect especially hyphal growth and the formation of haustoria and spores in oomycetes [22]. Since spores contain many ribosomes to support early growth stages, RNA synthesis is fully operational only after spore germination therefore, later development stages are most sensitive [19]. As a consequence of RNA inhibition, the precursors of RNA synthesis (i.e., nucleoside triphosphates) are accumulated. They activate j8-l,3-glucan synthetases, which are involved in cell wall formation [19] with the result that metalaxyl-treated hyphae often produce thicker cell walls than untreated ones. 

Several compounds may interfere with nucleic acid metabolism but commonly their effects are secondary to their primary mode of action, for example, the benzimidazoles. Compounds that inhibit nucleic acid biosynthesis directly are either phenylamides, pyrimidines or hydroxy-pyrimidines. Recently, the phenoxyquinolines were identified as exhibiting a novel mode of action in purine biosynthesis and are potentially useful fungicides. 

RNA Synthesis. The phenylamides comprise a diverse group of systemic compounds of which the acylalanines are the most successful (Figure 4.11). The acylalanine fungicides are systemic, mainly via the... 

In their studies the enzyme activity decreased when reagents were added that complex with thiols hence it was concluded that cysteine was probably the key enzymatic nucleophile. The production of this enzyme could be induced by exposure of the bacteria to various phenylamide- or phenylurea-containing herbicides and fungicides. The enzyme was also capable of hydrolyzing a variety of other phenylamides and phenylureas, albeit at somewhat different rates. 

Englehardt, G., P. R. Wallnofer, and R. Plapp, Purification and properties of an aryl acylamidase of Bacillus sphaericus, catalyzing the hydrolysis of various phenylamide herbicides and fungicides , Appl. Microbiol., 26,709-718 (1973). 

Knowledge on the structure of the receptor and the molecular interactions involved in binding of phenylamides is a prerequisite to understand their fungicidal action at the molecular level. Once a three-dimensional model of the receptor can be constructed, it may be possible to redesign phenylamide structures or even design completely new structures that fit into the binding site. 

Fungicides that interfere with nucleic acid synthesis are an important group of phenylamides that have kept a strong position in the Oomycete market despite major resistance problems (Table 12.6). Fungicides inhibiting adenosine-... 

A wide range of fungicides are available, both protectants (e.g. dithiocarbamates or oiganotins) and systemics, e.g. phenylamide group. Due to resistance problems, care should be taken with chemical choice and mixtures... 

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