Dorsey R. Mussell

Imidazole: Fungitoxic Derivatives

Study of several new types of fungitoxic derivatives of imidazole reveals that imidazoles substituted on the imine nitrogen atom are likely to be active if the substituent is electron-attracting, and if the atom connecting it to the imidazolyl moiety has tetrahedral geometry. Fungitoxicity is high with phosphinamidothionate and triarylmethyl groups as substituents. The presence of an asymmetric phosphorus atom in the substituent has no effect on fungitoxicity, but affects mammalian toxicity.

THE ACTIVITY OF 4,4′ ISOPROPYLIDENEBIS (2‐ISOPROPYLPHENOL) ON CECAL COCCIDIOSIS (EIMERIA TENELLA) IN CHICKENS

It is well known that successful chemotherapy of cecal coccidiosis of chickens depends upon recognition of the early symptoms of the disease in a flock. These early symptoms, however, are easily overlooked even by trained observers. In view of this fact, it is worth while to consider compounds which may be administered continuously as a protective measure to prevent severe Eimeria tefiella infections. Furthermore, such protective medication should permit the acquisition of a type of infection that will be conducive to the development of immunity. Use of the drug could be discontinued once immunity was established. The general concept of protective medication and concurrent development of immunity has been expressed by Farr and Allen,’ Swales,2 Goff,3 and, more recently, by Grumbles, Delaplane, and H i g g i n ~ . ~ The latter investigators have demonstrated the effectiveness of continuous medication with low concentrations of sulfaquinoxaline in the control of cecal and intestinal coccidiosis. A drug, considered from the standpoint of continuous feeding must be effective a t levels well below the threshold of toxicity. The concentrations employed must not interfere with the growth or thriftiness of a flock. Furthermore, it must be demonstrated that ingestion of the drug over long periods of time does not result in the deposition of substances in the tissues which might be potentially harmful to the consumer. Experiments performed in our laboratory have revealed that many compounds of the alkylidenediphenol type possesses significant anticoccidial action. In general, these materials are referred to as bisphenols or diphenols, and the compounds tested fall in two classes (FIGURE 1): (a) the 2,2’-methylenebisphenols; and (b) the 4,4’-alkylidenebisphenols. Previous investigators have reported that many compounds of this type possessed germicidal and fungicidal properties. Furthermore, Craige and Kleckner6 and Kerr6 have shown that certain chlorinated bisphenols administered to dogs and chickens were effective in the removal of tapeworms. More than 130 chemical variations involving these basic nuclei have been tested a t the Dow Chemical Company Biochemical Research Laboratory against Eimeria fenella in chickens. One of the most effective of these is 4,4’-isopropylidenebis(2-isopropylphenol) (FIGURE 2 ) . In the discussion which follows, this compound will be referred to by number as K6606 * The purpose of this report is to present evidence that continuous administration of K6606 (0.2-0.3 per cent) in the diet of growing chickens: (a) provides protection against cecal coccidiosis; (b) allows the development of measurable immunity to a challenging infection; ( c ) does not in-

New aspects of organophosphorus pesticides. VIII. Structure and fungitoxicity of organophosphorus compounds

Antifungal agents are used for a variety of purposes of several kinds. There is the necessity for prevention and treatment of mycotic diseases of man, of his animals, and of economically important plants. This may also require sterilization of part of the environment, for instance of soil or air. Furthermore, there are problems involving the preservation of valuable matter, such as foods, fibers, and certain other products.