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T Felcetto

Publications and source records attributed to T Felcetto.

6 recordsLinked to original sources
PubMed2006

Evaluation of broad-spectrum anthelmintic activity in a novel assay against Haemonchus contortus, Trichostrongylus colubriformis and T. sigmodontis in the gerbil Meriones unguiculatus.

The gerbil Meriones unguiculatus, infected with three species of nematodes, each located in a separate part of the gastrointestinal tract, provided a reliable laboratory assay for the evaluation of broad-spectrum anthelmintic activity. Gerbils harbouring 6-day-old infections of Haemonchus contortus, Trichostrongylus colubriformis and T. sigmodontis were given selected broad-spectrum anthelmintics by gavage. Three benzimidazoles, thiabendazole, oxfendazole and albendazole, a tetrahydropyrimidine, morantel, an imidazothiazole, levamisole hydrochloride, a macrocyclic lactone, ivermectin and an experimental natural product, paraherquamide, were active against all three nematodes at various dosages. Trichostrongylus colubriformis was most sensitive to levamisole hydrochloride, morantel, thiabendazole and paraherquamide whereas ivermectin, oxfendazole and albendazole were more effective against H. contortus. All compounds were active against the caecal nematode T. sigmodontis although it was less sensitive than T. colubriformis. Haemonchus contortus was more sensitive than T. sigmodontis to all anthelmintics tested except thiabendazole.

Albendazole↗
PubMed2005

Anthrax lethal factor inhibition.

The primary virulence factor of Bacillus anthracis is a secreted zinc-dependent metalloprotease toxin known as lethal factor (LF) that is lethal to the host through disruption of signaling pathways, cell destruction, and circulatory shock. Inhibition of this proteolytic-based LF toxemia could be expected to provide therapeutic value in combination with an antibiotic during and immediately after an active anthrax infection. Herein is shown the crystal structure of an intimate complex between a hydroxamate, (2R)-2-[(4-fluoro-3-methylphenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, and LF at the LF-active site. Most importantly, this molecular interaction between the hydroxamate and the LF active site resulted in (i) inhibited LF protease activity in an enzyme assay and protected macrophages against recombinant LF and protective antigen in a cell-based assay, (ii) 100% protection in a lethal mouse toxemia model against recombinant LF and protective antigen, (iii) approximately 50% survival advantage to mice given a lethal challenge of B. anthracis Sterne vegetative cells and to rabbits given a lethal challenge of B. anthracis Ames spores and doubled the mean time to death in those that died in both species, and (iv) 100% protection against B. anthracis spore challenge when used in combination therapy with ciprofloxacin in a rabbit "point of no return" model for which ciprofloxacin alone provided 50% protection. These results indicate that a small molecule, hydroxamate LF inhibitor, as revealed herein, can ameliorate the toxemia characteristic of an active B. anthracis infection and could be a vital adjunct to our ability to combat anthrax.

Animals↗
PubMed2004

Determination of poultry feed-through insecticide activity in an in vivo anticoccidial assay.

The ability of an in vivo anticoccidial assay to identify potential feed-through insecticides was demonstrated using first-instar Lucilia sericata on droppings from chicks fed medicated diets. Cyromazine, a commercially available feed-through insect growth regulator, ivermectin, diflubenzuron, fipronil, permethrin, and 2 experimental compounds were effective in varying degrees in killing L. sericata larvae. Eleven coccidiostats were effective against the protozoan parasites (Eimeria spp.) at commercially used levels, whereas they were ineffective against Lucilia larvae.

Animal Feed↗
PubMed2003

Isolation and insecticidal activity of mellamide from Aspergillus melleus.

Mellamide, a novel indole amide, was isolated from a fermentation of Aspergillus melleus using silica gel and high-performance liquid chromatographic methods. This allowed its separation from three known antiparasitic compounds (ochratoxin A, viomellin and xanthomegnin) also present in the potent extract. The structure was elucidated by (1)H, (13)C, COSY, DEPT, HMQC and HMBC NMR experiments. HR-FTMS aided in the molecular weight and formula determination. Mellamide showed in vitro insecticidal activity in bioassays against larvae of Lucilia sericata and Aedes egypti with LD(90) of 1,000 and 50 micro g/ml, respectively.

Amides↗
PubMed2002

Comparison of nodulisporic acid analogs in a Lucilia sericata in vitro assay and a Ctenocephalides felis membrane feeding system.

A medicinal chemistry program on the nodulisporic acid chemical class, guided by an artificial membrane flea-feeding assay, has recently identified permissive and nonpermissive regions of the pharmacophore for exploitation against fleas. This pathway was validated when several promising compounds from this program were administered orally to dogs at 15.0 mg/kg and found to have >90% flea activity for 2 wk. To determine if a surrogate insect assay would have provided the same guidance, a nodulisporic acid analog series was examined in both a Lucilia sericata larval assay and an artificial membrane flea-feeding assay using Ctenocephalides felis. Results from both insect assays were concordant in that even subtle chemical modification or substitution to the left-hand side of the nodulisporic acid pharmacophore resulted in substantial loss of insecticidal activity. Both assays were also in general agreement that the only modifications to the pharmacophore that did not result in loss of activity occurred to the C-8 side chain on the right-hand side of the molecule. Although there was good agreement between the 2 assays on the general regions of the pharmacophore, there was variance on individual compounds in the mono- and disubstituted amide series from the C-8 side chain. For example, the L. sericata assay showed several analogs from this subclass to possess similar activity to the parent acid, whereas the membrane assay indicated superior activity against fleas relative to the same parent. Consequently, although there was substantial general agreement between the assays, it was concluded that finer optimization of a lead compound should be done against the target parasite, even if it is ex vivo, as early as possible in a medicinal chemistry program.

Animals↗