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F C Peng

Publications and source records attributed to F C Peng.

10 recordsLinked to original sources
PubMed2001

Metabolism of territrem a in liver microsomes from wistar rats: 2. Sex differences and regulation with gonadal hormones and phenobarbital.

The aim of the present study was to assess the effects of sex difference on metabolism of territrem A (TRA) by liver microsomes from 7-wk-old Wistar rats. Metabolism of TRA to 2-dihydro-4beta-demethylterritrem A (MA2) through 4beta-hydroxymethyl-4beta-demethylterritrem A (MA1) and 4beta-oxo-4beta-demethylterritrem A (MAX) was observed in intact male rats. However, in intact female rats only MA1 was formed, although the amount of MA, formed in females was much less than in males. Phenobarbital pretreatment enhanced this step and was not affected by gonadectomy. In the gonadectomized rats of both sexes, MA2 was formed from TRA when the animals were further treated by testosterone and was significantly enhanced by treatment with phenobarbital. However, estradiol treatment or estradiol in combination with phenobarbital treatment did not affect MA2 formation from TRA in gonadectomized rats.

Animals↗
PubMed2001

Metabolism of territrem a by liver microsomes of Wistar rats: identification of the metabolites and their metabolic sequence.

The metabolism of territrem A (TRA) was investigated in liver microsomes of male Wistar rats. The results indicated that three metabolites were produced from TRA and these metabolic reactions were inhibited by metyrapone, an inhibitor of cytochrome P-450. Based on analysis by high-performance liquid chromatography (HPLC), mass, and nuclear magnetic resonance (NMR) spectroscopic techniques, the structure of these metabolites were identified as 4beta-hydroxymethyl-4beta-demethylterritrem A (MA1), 4beta-oxo-4beta-demethylterritrem A (MAX), and 2-dihydro-4beta-demethylterritrem A (MA2). It was proposed that reactions proceeded by three sequential oxidative reactions in the pyran moiety of TRA: first, hydroxylation at the 4beta-C methyl group of TRA to form MA1; second, oxidation at the 4beta hydroxyl group of MA, to form MAX; and third, decarbonylation at the 4beta-C oxo group of MAX to form MA2.

Animals↗
PubMed1999

Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism.

Territrem B (TRB) is a fungal metabolite isolated from Aspergillus terreus shown previously to be a potent and irreversible inhibitor of acetylcholinesterase (AChE). In the present study, a number of binding and inhibition assays were carried out to further characterize the inhibitory effect of TRB. The results indicate that the binding of TRB (a) is much more selective than a well characterized selective inhibitor of AChE, BW284C51, (b) adopts a one-to-one stoichiometry with the enzyme, (c) cannot be undone by an AChE-regenerating oxime agent, which contrasts the ability of 8 M urea to release AChE-bound TRB, (d) is enhanced by high concentration NaCl but prevented, unless preincubated, by Triton X-100, and (e) exhibits quasi-first order kinetics with an overall inhibition constant of 0.01 nM(-1) min(-1). Together these results suggest a very different irreversible binding (a noncovalent type) from that of the covalent type, which involves typical irreversible AChE inhibitors such as diisopropylfluorophosphate and neostigmine. According to the prediction of a molecular modeling study, the distinct AChE inhibitory characteristics of TRB may arise from the inhibitor being noncovalently trapped within a unique active-site gorge structure of the enzyme. It was predicted that an optimal TRB. AChE binding would position a narrowing connection of the TRB structure at a constricted area near the entrance of the gorge, thereby providing a structural basis for the observed irreversible binding.

Acetylcholinesterase↗
PubMed1997

Synthesis, structure and anti-acetylcholinesterase activity of 4beta-methoxymethyl-4beta-demethyl territrem B.

4beta-Methoxymethyl-4beta-demethyl territrem B [5] was synthesized from 4beta-hydroxymethyl-beta-demethyl territrem B [4] by treatment with dimethyl sulfate in methanolic NaOH. The structure of 5 was elucidated by uv, nmr and mass spectra. The IC50 of 5 on acetylcholinesterase (AChE) was 6.30 x 10(-5) M, which indicated 0.4% of the anti-AChE activity of territrem B [2].

Journal Article↗
PubMed1995

Acetylcholinesterase inhibition by territrem B derivatives.

Five derivatives of territrem B [2], a potent acetylcholinesterase inhibitor isolated from a rice culture of Aspergillus terreus, were prepared from 2 as well as from its major metabolite, 4 beta-hydroxymethyl-4 beta-demethylterritrem B [4]. The inhibitory activities of these derivatives against electric eel acetylcholinesterase (E.C. 3.1.1.7) were tested and it was concluded that the enone and the pyrone groups present in 2 may play an important biological role.

Animals↗
PubMed1994

Interactions of anticholinesterases with Achatina fulica acetylcholine responses and electrogenic sodium pump.

The dose-dependent effects of the anticholinesterases, neostigmine and mycotoxin territrem-B, were determined on: (i) Cl(-)-responses of voltage clamped Achatina fulica neurons to microperfused acetylcholine; (ii) the 4 K(+)-induced outward currents evoked by an electrogenic sodium pump in the same neuron; and (iii) acetylcholinesterase activity of Achatina fulica ganglionic homogenates. Both compounds at low doses potentiated the peak acetylcholine responses. However, they had different effects at higher (> 1 microM) doses in that neostigmine now antagonized acetylcholine responses, while territrem-B still produced a maximal potentiation. At all doses neostigmine produced a dose-dependent inhibition of acetylcholinesterase activity. The cholinolytic effect of high doses of neostigmine was associated with the inhibition of 4 K(+)-induced current in the same neuron, while territrem-B neither altered the K(+)-induced current nor antagonized acetylcholine responses. The cholinolytic effect of neostigmine was completely antagonized by the inhibition of electrogenic sodium pump by ouabain or by perfusion with K(+)-free solution. These results suggest that neostigmine at high concentrations inhibits the electrogenic sodium pump and that the cholinolytic effect of high doses of neostigmine is secondary to this action. Territrem-B, on the other hand, had no effect on the electrogenic sodium pump and had no effect on the neuronal membrane properties other than to inhibit acetylcholinesterase. Thus, territrem-B may be a useful tool for studying the interaction between acetylcholinesterase and acetylcholine receptors.

Acetylcholine↗
PubMed1985

Isolation, chemical structure, acute toxicity, and some physicochemical properties of territrem B' from Aspergillus terreus.

We have isolated a metabolite of territrem, designated territrem B', from the chloroform extract of a rice culture of Aspergillus terreus 23-1 by using the same isolation procedure as that for territrems A, B, and C. The present isolation procedure gave about 10 mg of territrem B' from 4 kg of rice culture per batch. Analysis of the high-resolution mass spectrum showed that the molecular composition of territrem B' is C29H34O10 (found, 542.2167; required, 542.200). Some results of physicochemical and acute tests are presented in this paper. Single-crystal X-ray diffractometry of territrem B' indicated that the three-dimensional structure of territrem B' has not changed significantly from that of territrem B except for the insertion of one oxygen atom into territrem B to make an additional pyron ring in the E ring. The tremorgenic activity of territrem B' is greatly reduced as tested by intraperitoneal injection in mice.

Animals↗