PubMed Health⌕ Search

Biomedical subjects

T R Fukuto

Publications and source records attributed to T R Fukuto.

At least 55 records · Page 3Linked to original sources

Relationships between the structure of organophosphorus compounds and their activity as acetylcholinesterase inhibitors.

This paper discusses the relation between chemical structure and inactivation of the enzyme acetylcholinesterase (AChE) by organophosphorus esters, in terms of reactivity and steric effects. The discussion is centered in organophosphorus esters of the type (R) (R') P(O) X, where X is a readily displaceable group and R and R' are various combinations of alkyl, alkoxy, alkylthio, and amido moieties. Specific examples illustrating the effect of AChE inhibition on the selective toxicity of organophosphorus esters for insects and mammals are also presented.

Animals↗

Carbamate resistance in mosquitos. The metabolism of propoxur by susceptible and resistant larvae of Culex pipiens fatigans.

Toxicity tests on Culex pipiens fatigans with propoxur (o-isopropoxyphenyl methylcarbamate) and carbofuran (2,2-dimethyl-2,3-dihydrobenzofuranyl-7-methylcarbamate) indicated that both compounds are fast-acting insecticides. Transfer of treated larvae to fresh water results in their partial recovery from knockdown.Propoxur is metabolized by resistant and susceptible larvae by their homogenate-reduced nicotinamide-adenine dinucleotide phosphate (NADPH(2)) enzyme system and by the microsome-plus-soluble fraction of mouse-liver extracts to at least 10 organosoluble metabolites with the isopropoxy group intact. The major metabolites, which are primarily hydroxylation products or the result of degradation of these products, have tentatively been identified as: acetone plus o-hydroxyphenyl methylcarbamate, 2-isopropoxy-5-hydroxyphenyl methylcarbamate, 2-isopropoxyphenyl carbamate, and 2-isopropoxyphenyl N-hydroxymethylcarbamate. Upon incubation of water-soluble products from treated larvae with beta-glucosidase, beta-glucuronidase, aryl sulfatase and acid phosphatase, the conjugates are hydrolysed, liberating mainly hydroxylated carbamates.The results indicate that slower absorption as well as faster detoxification by hydroxylation mechanisms, together with conjugation with polar molecules and elimination, are major factors in resistance of mosquito larvae to substituted-aryl methylcarbamate insecticides.

Animals↗

The comparative toxicity of DDT and analogues to susceptible and resistant houseflies and mosquitos.

Studies of the comparative toxicity of more than 120 DDT analogues to susceptible and insecticide-resistant houseflies (Musca domestica L.) and mosquitos (Culex fatigans Wiedemann and Anopheles albimanus Wiedemann) have shown that the relative effectiveness of these compounds against DDT-resistant insects is correlated with the susceptibility of the molecule to attack by DDT-ase at the benzylic hydrogen. Compounds highly effective against DDT-resistant flies and mosquitos are produced by blocking this detoxication mechanism by o-chlorination, alpha-fluorination, and by altering the aliphatic portion of the molecule as in the nitropropyl, neopentyl, dichlorocyclopropyl, and trichlorobenzanilide derivatives. These compounds offer practical possibilities for the control of DDT-resistant insects. The correlation of structure, DDT-like activity, and resistance ratios gives new insight into the mode of action of DDT and the nature of DDT resistance.

Animals↗