ACTIVITY:
Herbicide (anilide)
Note:
WHO:
believed obsolete or discontinued
CAS Name:
1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide
Structure:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2992524&dopt=Abstract
Biochem
Pharmacol 1985 Aug 15;34(16):2945-52
- Protonophoric
properties of fluorinated arylalkylsulfonamides. Observations
with perfluidone.
Olorunsogo OO, Malomo SO, Bababunmi
EA.
The acidity and lipophilicity of the fluorinated arylalkylsulphonamides
are determined by the nature of the substituents on their
aromatic rings. Herbicidal and anti-inflammatory effects of
these compounds appear to increase with their lipophilicity.
According to Mitchell's chemiosmotic theory, lipophilic weak-acid
uncoupling agents act by transporting protons across the inner
mitochondrial membrane and thus destroying the proton-electrochemical
potential gradient required for ATP synthesis and ion transport.
1:1:1-Trifluoro-N-[2-methyl-4-(phenylsulphonyl) phenyl]methanesulphonamide
(Perfluidone), a pre- and post-emergence herbicide (at 20
microM concentration), in isolated rat-liver mitochondria
caused
(1) a 2-fold stimulation of metabolic state-4 respiration,
(2) a reduction of respiratory control ratio (RCR) by at least
50%,
(3) an enhancement of latent ATPase activity by 40%,
(4) a significant passive swelling of mitochondria in 0.15
N NH4Cl(delta A520 = -0.46 +/- 0.003),
(5) proton intrusion during state-4 respiration (356 ng H+/min/mg
protein; ng H+/min/mg protein with 5 microM perfluidone),
and (6) at least 100% stimulation of oligomycin-inhibited
respiration.
These profiles are qualitatively comparable with those of
the classical lipophilic weak-acid uncoupler, carbonylcyanide-trifluoro-methoxyphenylene
hydrazone (FCCP), which acts by promoting the electrogenic
transport of H+ ions across mitochondrial membrane.
PMID: 2992524 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3160138&dopt=Abstract
Toxicology 1985 Jun 14;35(3):231-40
Sensitivity of oligomycin-inhibited respiration
of isolated rat liver mitochondria to perfluidone, a fluorinated
arylalkylsulfonamide.
Olorunsogo OO, Malomo SO.
Oxygen electrode polarographic measurements of the rate of
oxygen consumption by isolated rat liver mitochondria revealed
that oligomycin inhibition of respiration was offset to different
degrees by varying concentrations of perfluidone (1,1,1-trifluoro-N-(2
methyl-4-(phenylsulfonyl) methanesulfonamide). Using any of
pyruvate-malate, succinate or ascorbate-TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine)
as substrate, this herbicidal and anti-inflammatory agent
at 100 microM concentration caused a 5-fold stimulation of
oligomycin-inhibited respiration. Higher concentrations of
the herbicide (greater than or equal to 120 microM) gave lower
stimulatory effects. Similar stimulatory effects were obtained
with 1 microM FCCP (carbonylcyanide p-trifluoromethyoxyphenyl-hydrazone),
a classical protonophore. Our results also show an enhanced
oligomycin-sensitive ATPase action in intact mitochondria
incubated with ATP and varying concentrations of perfluidone.
Maximum enhancement effect (111.3%) was obtained at 120 microM
perfluidone. FCCP (1 microM) stimulated this ATPase action
by 130%. An initial inhibition of respiration by oligomycin
is due to an interaction with the proton well of FOF1-ATP
synthetase (Lardy, H.A. et al., Arch. Biochem. Biophys., 78
(1953) 587). Perfluidone probably increases the proton conductance
of mitochondrial inner membrane in the same manner as FCCP
and thus causes an increase in mitochondrial respiratory rate.
As protons move into the matrix, delta mu H+, the proton electrochemical
potential gradient becomes very small and the F0F1-ATP synthetase
functions in the direction of hydrolysis of ATP rather than
its shnthesis (Mitchell, P., Eur. J. Biochem., 95 (1979) 1).
These findings therefore indicate that
perfluidone acts in a way similar to FCCP, a classical uncoupler
and protonophore.
PMID:
3160138 [PubMed - indexed for MEDLINE]
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6238687&dopt=Abstract
Chem Biol
Interact 1984 Nov;52(1):67-78
Mitochondrial
bioenergetics during exposure of rats to perfluidone, a fluorinated
arylalkylsulphonamide.
Olorunsogo OO, Malomo SO.
Apart from the symptoms of poisoning which the fluorinated
arylalkylsulphonamides share with the classical protonphore
and uncoupler of oxidative phosphorylation, carbonylcyanide
p-trifluoromethoxyphenylhydrazone (FCCP), the direct correlation
between the lipophilic weak acid properties of these chemicals
and their biological activity suggests that permeation of
the inner mitochondrial membrane could be the initial step
in the molecular mechanism of their biological activity. Mitochondria
isolated from the livers of rats intraperitoneally exposed
to varying doses (0-80 mg/kg body wt.) of perfluidone (1,1,1-trifluoro-N-(2
methyl-4-(phenylsulphonyl)phenyl methanesulphonamide), a fluorinated
arylalkylsulphonamide pesticide, exhibit the following dose-dependent
features:
(i) increased state-4 respiration: stimulation being maximal
(greater than or equal to 400%) at 80 mg perfluidone per kg
body wt.),
(ii) release of respiratory control by ADP: least respiratory
control ratios (RCRs) (less than or equal to 1.2) were obtained
at 80 mg perfluidone per kg body wt.,
(iii) reduced ADP/O ratios,
(iv) increased mitochondrial passive swelling,
(vi) reduced rates of mitochondrial proton ejection during
succinate oxidation,
(vi) reduced rates of respiration-dependent Ca2+ accumulation
and
(vii) an enhanced oligomycin-sensitive ATPase action.
These features which are qualitatively identical to those
of the classical protonophore FCCP, suggest that permeation
of the inner mitochondrial membrane by perfluidone is accompanied
by a movement of protons into the matrix such that the proton
motive force required for ATP synthesis and ion transport
becomes small or not formed at all.
PMID: 6238687 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6673969&dopt=Abstract
- Eur J
Drug Metab Pharmacokinet 1983 Oct-Dec;8(4):321-7
Effect
of 1.1.1 trifluoro-N-(2-methyl-4-phenyl
sulfonyl) methane sulfonamide (Destun 50WP) on rat hepatic
microsomal enzymes, aniline hydroxylase and amino-pyrine
N-demethylase.
Thabrew MI, Emerole GO.
Investigations have been carried out to determine the effects
of the herbicide 1.1.1 trifluoro-N-(2-methyl-4-phenyl sulfonyl)
methane sulfonamide (Destun) on some hepatic microsomal
drug metabolizing enzymes in rat. Administration of 100
mg herbicide/kg rat (i.p. or oral) resulted in a stimulation
of aniline hydroxylase and p-aminopyrene N-demethylase activities
by 1.3 fold and 1.6 fold respectively. A dose-related increase
in enzyme activities was observed with a maximum effect
at about 100 mg Destun/kg rat. The increased microsomal
protein content, liver weight: body weight ratio and decreased
sleeping time in the herbicide-treated animals indicated
the possibility of Destun being an "inducer". Results of
investigations on the kinetic properties of aniline hydroxylase
and p-aminopyrene-N-demethylase on administration of Destun
suggests that in addition to its inducer effect, the herbicide
could stimulate the enzyme activities by decreasing the
affinity of these enzymes for their respective substrates.
PMID: 6673969 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6677469&dopt=Abstract
-
- Dev
Toxicol Environ Sci 1983;11:345-8
-
- Perfluidone,
a fluorinated arylalkylsulphonamide carries
protons across mitochondrial coupling membrane.
Olorunsogo OO, Malomo SO, Bababunmi
EA.
PMID: 6677469 [PubMed - indexed for MEDLINE]
-
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6133695&dopt=Abstract
-
- Comp
Biochem Physiol C 1983;74(2):473-6
-
- Species
variations in the sensitivity of the endoplasmic reticulum
to the herbicide 1.1.1. trifluoro-N-(2-methyl-4-phenyl sulfonyl
phenyl) methane sulfonamide.
Thabrew MI, Emerole GO.
1. The effects of the herbicide 1.1.1. trifluoro-N-(2-methyl-4-phenyl
sulfonyl phenyl) methane sulfonamide on the drug metabolising
enzyme activities in livers of rat, mouse and guinea pig
have been compared.
2. In all three animal models, the herbicide increased the
activities of both aniline hydroxylase and p-aminopyrine
demethylase. The greatest inductive
effect was seen in the rat, while the least effect
was evident in the guinea pig.
3. In mouse and guinea pig, 1.1.1. trifluoro-N-(2-methyl-4-phenyl
sulfonyl phenyl) methane sulfonamide had no effect on the
soluble or microsomal epoxide hydratases or the glutathione
S-transferases. In the rat, however, the herbicide significantly
decreased the microsomal epoxide hydratase activity, as
well as the soluble and microsomal glutathione S-transferase
activities.
4. These results are discussed in relation to factors responsible
for species differences in the response to foreign compounds.
PMID: 6133695 [PubMed - indexed for MEDLINE]
From
Toxline at Toxnet
- Pestic. Biochem. Physiol. 7(1): 62-72; 1977.(7
references)
-
- Herbicide perfluidone (1,1,1-trifluoro-N-
(2-methyl-4- (phenylsulfonyl)phenyl) methanesulfonamide):
its metabolism in rats and chickens.
Paulson GD, Jacobsen AM, Zaylskie RG
PESTAB. Rats and chickens were each given a single oral
dose (10 or 100 mg/kg body wt) of 1,1,1-trifluoro-N- (2-methyl-4-
(phenylsulfonyl)phenyl- 14C(UO)methanesulfonamide ((14C)perfluidone).
Depending on the size of the dose, from 8.4 to 36.2% of the
[14C) was eliminated in the urine and from 36.4 to 85.4% was
eliminated in the feces within 48 hr after dosing. Less than
1% of the (14C) given to laying hens at (14C)perfluidone was
present in the eggs produced during the first 96 hr after
dosing. The percentage of the administered (14C) that remained
in these animals (body with G.I. tract and contents removed)
varied from 0.34 (96 hr after dosing) to 1.68% (48 hr after
dosing). 14C-labeled compounds in the urine and feces from
the rats and chickens were purified by solvent extraction,
column chromatography, and gas-liquid chromatography, and
then identified by infrared and mass spectrometry. The parent
compound was the major 14C-labeled component in the urine
and feces of both animals. 1,1,1-Trifluoro-N- (2-methyl-4-
(3-hydroxyphenylsulfonyl) phenyl) methanesulfonamide was present
in the feces of both animals. The proposed structures of other
metabolites were 1,1,1-trifluoro-N- hydroxy-N- (2-methyl-4-
(phenylsulfonyl) phenyl) methanesulfonamide (rat urine) and
1,1,1-trifluoro-N- (2methyl-4- ((methylsulfonyl)-phenylsulfonyl)
phenyl methanesulfonamide (chicken urine).
-
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=853723&dopt=Abstract
-
- J Sci
Food Agric 1977 Feb;28(2):180-4
-
- Stimulation
of the activity of the IAA-oxidising enzyme system in Lens
culinaris roots by dalapon and perfluidone.
Tafuri F, Businelli M, Scarponi L, Marucchini
C.
PMID: 853723 [PubMed - indexed for MEDLINE]
From
Toxline at Toxnet
J Agric
Food Chem 1975 Sep-Oct;23(5):869-72
- Metabolic
fate of perfluidone
herbicide in a lactating cow.
Ivie GW.
PESTAB. Perfluidone (1,1,1-trifluoro-N- (2-methyl-4-
(phenylsulfonyl) phenyl-14C) methanesulfonamide) was administered
at 5 mg/kg as a single oral dose to a lactating cow. Radiocarbon
was rapidly and essentially quantitatively excreted during
a 7-day post-treatment period. About 80% of the administered
dose appeared in urine, about 20% was recovered in feces,
and only 0.1% of the dose was secreted into the milk. Unmetabolized
perfluidone accounted for 90-95% of the total radiocarbon
present in the urine and milk, and the remaining radioactivity
was mainly in the form of two metabolites hydroxylated at
the 3 or 4 positions of the phenylsulfonyl ring. These products
were excreted almost totally in nonconjugated form. The major
urinary metabolite and the only milk metabolite was 4-hydroxyperfluidone,
whereas perfluidone and its 3-OH and 4-OH derivatives occurred
in approximately equal amounts in feces. (Author abstract
reprinted by permission of the American Chemical Society)
- From
Toxline at Toxnet
-
- Weed Sci. 23(5): 344-348; 1975.(16
references)
-
- Persistence and movement of perfluidone
in soil.
Ketchersid ML, Merkle MG
PESTAB. Perfluidone (1,1,1-trifluoro- N-)2-methyl-4- (phenylsulfonyl)
phenyl(-methanesulfonamide) was chemically stable for 2 to
3 weeks on the surface of three Texas soils either air dry
or at field capacity and at temperatures of 22 and 46DEG C.
Perfluidone was susceptible to photodecomposition when applied
to
- glass petri dishes and exposed to ultraviolet irradiation.
Perfluidone was readily leached through neutral or slightly
alkaline soils, with a tendency toward greater downward movement
in soils having low clay and organic matter content. However,
leaching was less in an acid loamy sand than in either neutral
loamy sand or clay soils. (Author abstract by permission)
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