Diamphenethide—a new fasciolicide active against immature parasites

Harfenist, M.

doi:10.1002/ps.2780040615

Cited by 25 publications

(3 citation statements)

References 4 publications

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“…Of those fasciolicides tested in this study, only diamphenethide showed no in vitro activity. This result was not unexpected because the activity of this compound against flukes in sheep has been ascribed to its free-amine metabolite (Harfenist, 1973). Clearly, the flukes themselves did not deacetylate this compound under in vitro conditions but it would appear that deacetylation did occur in the presence of rabbit liver homogenate or microsomes.…”

Section: Discussionmentioning

confidence: 86%

Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium

1987

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The cidal properties of some phenolic, halogenated diphenyl, salicylanilide, benzimidazole and diaminophenoxyalkane anthelmintics, against 6-week-old worms of Fasciola hepatica were assessed in vitro. In a conventional fluke culture medium containing RPMI 1640, supplemented with serum with or without rabbit erythrocytes or pink-ghosts, only the halogenated diphenyl and salicylanilide compounds showed activity at concentrations equal to or less than 100 microM. However, when basal, serum and cell-free RPMI 1640 was used, all compounds other than diamphenethide were highly active, their minimum lethal concentrations being some 25-125 times lower under these conditions. The inclusion of rabbit liver microsomes in the basal culture medium resulted in diamphenethide exhibiting cidal activity equivalent to that seen when its free-amine active metabolite was assayed. The possibility that the activity of many of these compounds was masked in vitro because of their serum binding properties is discussed. Recommendations are made that in vitro screens for new fasciolicides should be carried out in serum-free medium and that additional replicates containing mammalian liver microsomes and liver cytosolic extracts be included as means for the metabolic activation of certain otherwise undetectable prodrugs.

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Section: Discussionmentioning

confidence: 86%

Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium

1987

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“…The organic layer was dried over MgSO 4 , concentrated in vacuo with the residue, adsorbed onto silica (∼1.00 g), and purified by flash chromatography (2% CH 3 OH in CH 2 Cl 2 ) to afford the title compound (0.067 g, 65%) as a white solid (mp 158–164 °C). 46 …”

Section: Methodsmentioning

confidence: 99%

“…The reaction mixture was then stirred at room temperature for 16 h. The resulting reaction mixture was then concentrated in vacuo, diluted with ethyl acetate (100 mL), washed with water (2 × 100 mL), and saturated with NaHCO 3 (100 mL). The organic layer was dried over MgSO 4 , concentrated in vacuo with the residue, adsorbed onto silica (∼1.00 g), and purified by flash chromatography (2% CH 3 OH in CH 2 Cl 2 ) to afford the title compound (0.067 g, 65%) as a white solid (mp 158–164 °C) …”

Section: Methodsmentioning

confidence: 99%

Small-Molecule Inhibitors of the NusB–NusE Protein–Protein Interaction with Antibiotic Activity

Cossar¹,

Abdel-Hamid

Ma³

et al. 2017

ACS Omega

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The NusB–NusE protein–protein interaction (PPI) is critical to the formation of stable antitermination complexes required for stable RNA transcription in all bacteria. This PPI is an emerging antibacterial drug target. Pharmacophore-based screening of the mini-Maybridge compound library (56 000 molecules) identified N,N′-[1,4-butanediylbis(oxy-4,1-phenylene)]bis(N-ethyl)urea 1 as a lead of interest. Competitive enzyme-linked immunosorbent assay screening validated 1 as a 20 μM potent inhibitor of NusB–NusE. Four focused compound libraries based on 1, comprising 34 compounds in total were designed, synthesized, and evaluated as NusB–NusE PPI inhibitors. Ten analogues displayed NusB–NusE PPI inhibition ≥50% at 25 μM concentration in vitro. In contrast to representative Gram-negative Escherichia coli and Gram-positive Bacillus subtilis species, these analogues showed up to 100% growth inhibition at 200 μM. 2-((Z)-4-(((Z)-4-(4-((E)-(Carbamimidoylimino)methyl)phenoxy)but-2-en-1-yl)oxy)benzylidene)hydrazine-1-carboximidamide 22 showed excellent activity against important pathogens. With minimum inhibitory concentration values of ≤3 μg/mL for Gram-positive Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus and ≤51 μg/mL for Gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, 22 is a potent lead for a novel antibacterial target. Epifluorescence studies in live bacteria were consistent with 22, inhibiting the NusB–NusE PPI as proposed.

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Polyimides containing oxyethylene units

Feld

Ramalingam

Harris

1983

J. Polym. Sci. Polym. Chem. Ed.

124

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Four aromatic dinitro compounds containing oxyethylene units 1,2‐bis(4‐nitrophenoxy)ethane, bis(2)‐(4‐nitrophenoxy)ethyl ether, 1,2‐bis(2)‐(4‐nitrophenoxy)ethoxy)ethane, and bis(2‐(2‐(4‐nitrophenoxy)ethoxy)ethyl) ether were prepared by an aromatic nucleophilic substitution reaction that involved 1‐fluoro‐4‐nitrobenzene and the appropriate oxyethylene glycol. Each of the dinitro compounds could be reduced chemically or catalytically to produce the diamines 1,2‐bis(4‐aminophenoxy)ethane, bis(2‐(4‐amino‐phenoxy)ethyl ether, 1,2‐bis(2‐(4‐aminophenoxy)ethoxy)ethane, and bis(2‐(2‐(4‐aminophenoxy)ethoxy)ethyl) ether. Polymerization of the diamines was carried out in m‐cresol with toluene as an azeotroping agent. Polymides derived from 5,5′‐[2,2,2‐trifluoro‐1‐(trifluoromethyl)ethylidene]bis‐1,3‐isobenzofuradione exhibited good solubility in chlorinated solvents, glass transition temperatures as low as 140°C, as evidenced by viscous flow, and good thermal stability; a 5% weight loss generally occured at greater than 450°C. Isothermal aging studies conducted at 600°F(315°C) for 200 h indicated that weight loss is directly related to oxyalkylene chain length–10% for the shortest and 50% for the longest chain.

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Diamphenethide—a new fasciolicide active against immature parasites

Cited by 25 publications

References 4 publications

Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium

Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium

Small-Molecule Inhibitors of the NusB–NusE Protein–Protein Interaction with Antibiotic Activity

Polyimides containing oxyethylene units

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