GB2035087A - Agents for the chemotherapy of virus diseases in cultivated plants - Google Patents

Abstract

A composition for the chemotherapy of virus diseases of cultivated plants, comprising a compound of the following general formula <IMAGE> in which R1, R2, R3, and/or R4 represent: hydrogen, hydroxy-, carboxy-, nitro-, and/or alkoxy groups or substituted alkyl-, alkenyl-, cycloalkyl-, aryl-, and/or aralkyl radicals, R4 additionally represents: ureido-, ureidoalkyl-, carbamoyl groups unsubstituted or substituted by alkyl-, alkenyl-, or aryl radicals; and amino- or alkylidene-, or benzylidene amino radicals; R1 and R2 or R3 and R4 together may form a ring; and R1, R2, R3 and R4 must not be identical. <IMAGE>

Description

SPECIFICATION Agents for the chemotherapy of virus diseases in cultivated plants The invention relates to agents for the chemotherapy of virus diseases of cultivated plants, that is to say, "the use of substances which to a specific extent retard or inhibit the propagation of viruses or the development of disease in cultivated plants" (M.Klinkowski, Pflanzliche Virologie, Berlin 1967, page 283). This renders it possible to stabilise the yield of virus-infected or virusendangered cultures. This is essential from the viewpoint of economy since, in a large number of cultivated plants, virus diseases cause considerable losses of yield which are occasioned both by a qualitative and quantitative reduction in the produce harvested. Thus, for example, potatoes are infested by 29 types of virus in Europe (K. Schmelzer and P.Wolf, Wirtspflanzen der Viren and Virosen Europas, Nova Acta Leopoldina, 36, 1971, Supplementum 2, 262 S.). Some of these viruses such as leaf roll virus and the virus causing streak disease in potatoes, reduce the possible yield of tuberous crop up to more than 90% in the case of heavily diseased plants. In the case of beet, such as sugar beet, virus diseases, particularly the virulent beet yellowing, also cause annular losses affecting both the beet mass and the sugar content. In many countries, virus diseases also cause heavy losses in the yield of grain. As in many other countries, fodder legumes such as lucern, lupine and horse beans, and granular legumes such as peas or beans, are attached in the GDR by a large number of viruses which cause considerable losses in these protein-rich cultures which are particularly suitable for closing the protein gap.Viruses also cause considerable damage in the cultivation of vegetables, in the cultivation of medicinal herbs, fragment plants and luxury plants, in fruit-growing and in the cultivation of ornamental plants.

In view of the many virus diseases occurring in a large number of host plants, it is also essential to have chemical preparations available which render it possible to control plant viruses and thus to close the gap between the control of viruses and the control of insects or fungi which damage plants and against which it has been possible, in recent decades, to develop a large number of highly effective preparations.

Characteristic of the known methods of controlling virus diseases in plants and for reducing the damage caused by viruses are the following: At the present time, indirect measures are basically used for controlling virus diseases in plants. The first method to be mentioned is that of culling virus-infected plants or virus-infected vegetable matter. Selective methods of this type are primarily intended to eliminate sources of infection which can rapidly infect the entire crop with viruses. Since virus diseases of plants frequently have unrecognizable symptons, corresponding selective methods frequently require expensive virus tests such as eye layer tests in the case of potatoes, tests with indicator plants or serological tests. Owing to the high cost, generally only valuable cultivated material can be tested by means of such tests.

Further indirect methods which may be mentioned are methods of controlling virustransmitting insects by suitable insecticides. Even these methods are only partially successful.

Primarily, the propagation of persistent viruses, that is to say, the viruses which the insect can transmit during the rest of its lifetime when it has become infectious approximately 1 to 3 hours after picking up the virus, is limited to a greater or lesser extent. In contrast to this, the propagation of non-persistent viruses by insecticide treatment can be prevented to a far lesser extent, and it is impossible to prevent the propagation of mechanically transmissible viruses. In order to close this gap at least partially, attempts have been made to limit the transmission of non-persistent viruses by coating the plants to be protected with a film of skimmed milk or dispersed oils. Measure of this type have generally not proved to be fully effective and are too expensive for most cultures.

Meristem culture may be mentioned as a method of freeing plants from viruses. This method is based on the fact that viruses do not usually increase in rapidly dividing meristematic tissue.

When the vegetation cones (= the meristems) of the virus-infected plants are carefully separated from the latter and transferred to suitable nutritive soils under sterile conditions, healthy plants very frequently develop from them. The increase of some viruses can also be limited by heat therapy, that is to say, by rearing virus-infected plants at very high temperatures.

Heat thereapy is frequently used in conjunction with the meristem culture. Owing to the high cost involved, the two methods can only be used to a very limited extent in the case of valuable cultivated material. Moreover, their effect is unreliable.

Premunition (i.e. relative immunity) can offer limited protection against losses of yield in horticultural crops, particularly in green-houses. Premunition means the infection of cultivated plants by a virus strain of very low virulence which causes very little damage but which prevents infection of the correspondingly premunised plants by an agressive strain of the same type. One of the disadvantages of corresponding methods is that mixed infections can be caused in the case of super-infection by a different type of virus and cause considerable economic losses. This is particularly the case when the plant cultures, used to obtain the virus material used for premunition, are spontaneously infected by a second virus which is then transmissible during premunition to all the plants to be protected. Furthermore, premunition is only possible in the case of a few virus diseases.

In these circumstancs, it is desirable to provide methods and agents which render possible the chemotherapy of virus-infected plants in the same manner as is readily possible by treatment with suitable chemical preparations in the case of plants infected by fungi and, to a limited extent, in the case of plants infected by bacteria. With this object in view, the antiphytoviral effect of basic analogues such as 8-azaguanine or thiouracil and anti-biotics has been tested, particularly in isolated pieces of tissue, without finding any practical and economically justifiable solutions. The use of vegetable matter herbicides (such as 4-chloro-2-methyl- phenoxy acetic acid or 2,4-dichloro-phenoxy acetic acid) and nitrosophenols (4-nitrosophenol, 1-nitroso-2naphthol-2) also did not provide the desired solution.Only the chemotherapeutic efficacy of some hexahydrotrizaines could be confirmed in field tests. However, the stage thus reached does not provide a solution to all the problems arising in the chemotherapy of virus diseases of plants. The problem of resistance may be especially mentioned in this connection.

The object of the invention is to improve the known agents and methods, which are expensive and frequently unreliable, for controlling viruses on cultivated plants, substantially to reduce the high labour costs, and to provide an economically advantageous solution to the problem of virus control which is not only confined to selected cultivated material but which can be applied to a large extent in the production of plant crops and reliably stabilises the yields of cultivated plant crops.

The object of the invention is to find effective chemical substances which, by virtue of their chemical constitution, render antiviral therapy possible. At the same time, they are to be suitable for widening the spectrum of chemotherapeutically controllable plant viruses and to counteract resistance phenomena relative to chemotherapeutics which rapidly appeared in antibacterial thereapy after the discovery of the first antibiotics and which are to anticipated in antiviral thereapy in view of the high degree of mutability of viruses. By way of example, this can be achieved by making available a selection of antiviral preparations which are used alternately.

In accordance with the invention, this object is achieved by using, for the purpose of controlling virus diseases in plants, agents which contain compounds of general formula I

in which R1, R2, R3 and/or R4 represent: Hydrogen, hydroxy-, carboxy-, nitro- and/or alkoxy groups as well as substituted alkyl-, alkenyl-, cycloalkyl-, aryl- and/or aralkyl radicals and R4 additionally represents: ureido-, ureidoalkyl-, carbamoyl groups optionally substituted by alkyl-, alkenyl-, or aryl radicals and amino- or optionally substituted alkylidene- or benzylidene amino radicals. Suitable substituents of the said hydrocarbon radicals which, if required, can appear several times, are, for example: hydroxy-, carboxy-, amino-, nitro-, alkoxy groups as well as chlorine or alkyl radicals.

R,, R2, R3 and R4 must not be identical in a compound, and R, and R2 or R3 and R4 can also close to form a ring, such as

The agents can contain diluents and, if required, further additives in addition to the compounds, in accordance with the invention, of general formula 1. Surfactants, adhesives and/or further formulation agents can be added. The antiviral efficacy of both combination partners is considerably increased by combinations with other compounds having a more or less pronounced antiviral effect, or with growth regulators.

The compunds in accordance with the invention have a pronounced antiviral action particularly with respect to economically important virus diseases of potatoes such as leaf roll disease of potatoes (causative organism: potato leaf roll virus), streak disease of potatoes (causative organism: potato Y virus) and various mosaic diseases (causative organism: inter alia, potato X virus and potato A virus). Furthermore it is possible to control the yellowing disease of beet, brome grass mosaic on barley and grasses and other virus diseases of grain, cucumber mosaic and various virus diseases of vegetable plants and luxury plants such as tomatoes and tobacco, and of decorative plants such as dahlias.

The selection of virus strains resistant to chemotherapeutica can be counteracted by the alternate or combined use of various antiphytoviral preparations.

Quantities of from 0.5 to 10 kg/ha are generally sufficient to provide adequate protection against loss of yield.

The agents in accordance with the invention can be formulated and applied by the known, conventional methods. Thus, inert diluents and suitable formulation agents can be added to the effective substances and the mixture can be processed to form spray powders, pastes, emulsion concentrates etc. It has proved to be advantageous if the effective substance content amounts to 10 to 90% of the agent, and, shortly before use, is dispersed with water to form spray liquors or, in the case of satisfactorily water-soluble compounds, to form spray solutions. The spray liquors and spray solutions can be applied by conventional sprayers. With appropriate formulation, the compounds in accordance with the invention are particularly suitable for combining the herbicides, insecticides, fungicides and other plant protection agents in tank mixtures.

Examples Whole plant tests on Solanaceae were primarily used for the purpose of characterising the antiphytoviral effects of the urea compounds in accordance with the invention. The tests viruses used were plant viruses which frequently occur and, on the one hand, systematically infect the host and, on the other hand, render it possible satisfactorily to determine the concentration by serological methods. In the fundamental experiment, the two lower intact leaves of plants of nicotiana tabacum "Samsun", which had formed 5 to 7 leaves, were inoculated with potato X virus with the use of an abrasive (carborundum powder, grain size 500).Two days before and two days after inoculation, the test plants were sprayed to dripping wetness with a solvent-water mixture which generally contained (= if not stated otherwise) 5 X 10-3 mol/l of the effective substance to be tested, and 25% fekama adhesive (adhesive based on buna latex.) Under practical conditions, this corresponds to the application of 600 1 of spray solution or liquor per hectare of field area. A number of plants were inoculated with the same virus in the manner described for control purposes. Spraying was effected with the same solvent-water mixture with the addition of 0.2% fekama adhesive, but without effective substance.

With the use of the dilution end point determination (geometrical dilution in each case in the ratio 1:1 with physiological solution of common salt until no more virus is detectable serologically), the virus concentration in leaves of a higher series, which were separated from the uppermost inoculated leaf by at least 2 leaves, was ascertained serologically and separately in the plants and leaves by the precipitation drop test 14 to 20 days after inoculation (G. Schuster, Archiv Phytopath.u. Pflanzenschutz 7, 1971, 171-187u. 13, 1977, 231-141). Each test section comprised at least 10 individual plants.

The virus concentration found in the leaves of the individual plants was expressed in numerical values. The numerical value 0 means that no virus was detectable even in the ratio 1:1 of diluted (= starting) expressed sap. The numerical value 1 means that no more virus was detectable after diluting once in the ratio 1:1, and the numerical value 2 means that no virus precipitate appeared after diluting twice, etc. For the purpose of comparing the results obtained in the test sections with those of the control, the corresponding antilogarithms were formed from the individual numerical values which, corresponding to the described test arrangement, represent logarithms (exponents) to the base 2. The antilogarithms were averaged and compared with the corresponding average values found in the case of the control plants.The following Tables show the percentage of the virus concentration which was found in the test section compared with the control (control = 100%). This value is designated "reduction coefficient (RC)." By way of example, RC = 8 means that the average virus concentration in the test section was reduced to 8%.

The significance of the differences found was checked by the student's t-test. The test result was given in symbols adjacent to the differences expressed in percentages. The symbols signify the following: :p 5% + : 5% p 1% + + :1% = p 0.1% + + + :0-i% = p kp = probability of exceeding The experiments conducted and evaluated in the manner described produced the following results in the case of the following urea compounds selected by way of example: Test series A Compound and concentration Solvent RC and significance NH2. CO. NHOH, 10-2 mol/l H2Q 44++ NH2 . CO . NH. CH3, 0.1% H20 74# NH2. CO. NH. CH2. NH.CO.NH2,0.1% H20 50 + NH2. CO . NH . CO .NH2, 0.1% H20 67* C6H5. NH . CO. NH . C6H5, A 3% 57 + 10-2 mol/l A 5% 53++ 5 X 10-3 mol/l o-(NH2. CO. NH)2. C6H4 H20 52+ 5 X 10-2 mol/l A = acetone Test series B In the methodology described, the antiviral effects of the ureas in accordance with the invention were tested in various virus host combinations. The following examples show that the compounds have efficacy spectra which render possible an effective antiviral chemotherapy in the case of a large number of virus diseases of important cultivated plants.

Compound, concentration Virus Host RC and significance and solvent Methylene bisurea Potato X virus Nicotiana 43+ + 10-2 mol/l in H20 tabacum 'Samsun' (Virginia tobacco) Nicotiana 51 + + glutinosa (tobacco) Lycopersicum 41 + esculentum (tomato) Potato Y virus Nicotiana 47 tabacum 'Samsum' (Virginia tobacco) Arabis mosaic Cucumis 67+ virus sativus (cucumber) N-phenyl-N'(m) carboxy Tabacco mosaic Nicotiana 45+ + + phenyl urea virus glutinosa 5 X 10-3 mol/l in H20 Potato X virus N. tabacum 65+ 'Samsun' (Virginia tobacco) Lycopersicum 69+ esculentum (tomato) Potato Y virus N. tabacum 59' 'Samsun' (Virginia tobacco) Arabis mosaic Cucumis 73 virus sativus (cucumber) Test series C In the methodology described, the ureas in accordance with the invention were applied to plants combined with growth regulators, herbicides, fungicides, biologically active, particularly antivirally effective heterocyclic compounds containing N and/or 0, and other biologically active substances.The following examples, in which the substances were applied once individually and once combined, namely in the same concentration as in the individual application, to plants of Nicotiana tabacum 'Samsun' infected with the potato X virus, show that, in combinations, the antiphytoviral effect of the combination partners is increased:: Urea preparation RC and signifi- Combination RC and Combination (A) and conc. cance partner (B) signifi- RC and signifi and conc. cance cance Methylene 72* Ethylene (2bisurea chloroethyl 88 24+ 10-2 mol/l phosphonic acid)0.02 Chloro- 79+ 50+ propionic acid 0.05% Tetrahydro-2, 67+ 30++ 4-methyl oxazine 0.01% 2,4-diphenyl-6- 50+ 18+++ hydroxy-s triazine 2 x 10-2 mol/l 1-ss-D-ribo- 51+ 0+++ furanosyl 1 ,2,4-triazole carboxamide 0.001% Methyl biuret 69+ Ethylene (2- 88 48+ chloro-ethyl phosphonic acid 0.02% 1 -ssD-ribo- 28++ 0+++ furanosyl 1 2,4-triazole- carboxamide 0.001% N-phenyl-N'(m)- 57+ a-[4 Chloro-2- 91 31 ++ carboxyphenyl- methylphenoxyl]urea propionic acid 5 x 10-3 mol/l 2 X 10-5mol/l

Claims (10)

1. A composition for the chemotherapy of virus diseases of cultivated plants, comprising a compound of the following general formula

in which R1, R2, R2, and/or R4 represent: hydrogen, hydroxy-, carboxy-, nitro-, and/or alkoxy groups or substituted alkyl-, alkenyl-, cycloalkyl-, aryl-, and/or aralkyl radicals, R4 additionally represents: ureido-, ureidoalkyl-, carbamoyl groups unsubstituted or substituted by alkyl-, alkenyl-, or aryl radicals; and amino- or alkylidene-, or benzylidene amino radicals; R, and R2 or R3 and R4 together may form a ring; and R1, R2, R3 and R4 must not be identical.

2. A composition as claimed in claim 1 in which the substituent in the substituted hydrocarbon radical is at least one hydroxy-, carboxy-, amino-, ureido-, nitro-, alkoxy-, chloro-or alkyl radical.

3. A composition as claimed in claim 1 or claim 2 which also contains one or more solvents, diluents and, if required, further conventional additives.

4. A composition as claimed in any one of claims 1 to 3 which also contains one or more surfactants, adhesives and/or further formulation agents.

5. A composition as claimed in any one of claims 1 to 4 in which the compound of the general formula is present in combination with plant hormones, synthetic plant growth regulators, aryl- or alkyl-substituted carboxylic acids and/or biologically active heterocyclic compounds containing N and/or 0 corresponding to test series C whereby the antiphytoviral effect of the two combination partners is increased and the spectrum of the controllable virus diseases is widened.

6. A composition as claimed in claim 5 in which the heterocyclic compound is an oxazine or triazole.

7. A composition as claimed in any one of claims 1 to 6 in which the compound of the general formula comprises 10 to 90% be weight of the composition.

8. The use in the control of virus diseases in cultivated plants of a compound as defined in claim 1.

9. A method of controlling virus disease in cultivated plants which comprises applying thereto a composition as claimed in any one of claims 1 to 7.

10. A composition as claimed in claim 1 and substantially as hereinbefore described with reference to any one of the Examples.