Benfluron hydrochloride

Mĕlka, M; Krepelka, J.

doi:10.1358/dof.1987.012.08.74459

Cited by 14 publications

(5 citation statements)

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“…The fact that benfluron had been previously studied as a cytostatic agent [14] suggested that the therapeutic index of the compound could be a key consideration for optimization. To test this hypothesis, we first evaluated the selectivity of the molecule in peripheral blood mononuclear cells (PMBCs), the natural host of the virus, obtaining antiviral EC 50 and cytotoxic CC 50 values of 5.5 and of 7.1 µM, respectively (Figure S1).…”

Section: Optimization Strategymentioning

confidence: 99%

Exploring the HIV-1 Rev Recognition Element (RRE)–Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

Chumillas,

Loharch,

Beltrán

et al. 2023

Molecules

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Human immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE–Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE–Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE–Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function.

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Section: Optimization Strategymentioning

confidence: 99%

Exploring the HIV-1 Rev Recognition Element (RRE)–Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

Chumillas,

Loharch,

Beltrán

et al. 2023

Molecules

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“…The starting structure from the group of basic benzo[c]fluorene derivatives, benfluron (5-(2-dimethylaminoethoxy)-7H-benzo[c]fluoren-7-one hydrochloride [2][3][4]), exhibited an interesting spectrum of pharmacodynamic properties in experiments carried out in vitro and in vivo [5][6][7][8]. The disposition of benfluron in experimental animals was studied by TLC [9][10][11][12], HPLC [13][14][15], MS [16] and NMR [17] methods using a comparison of the metabolites with their synthesized standards [18,19].…”

Section: Introductionmentioning

confidence: 99%

Disposition study of a new potential antineoplastic agent dimefluron in rats using high-performance liquid chromatography with ultraviolet and mass spectrometric detection

Cisar

Nobilis

Vybíralová

et al. 2005

Journal of Pharmaceutical and Biomedical Analysis

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“…Benfluron [5-(2-dimethylaminoethoxy)-7-oxo-7H-benzo[c]fluorene hydrochloride] is a potential antineoplastic agent (5,6) exhibiting interesting pharmacodynamic properties in experiments carried out in vitro (in animal and human cells) and in vivo (2,9,10,11). Biotransformation of benfluron was also studied with the use of experimental in vivo and in vitro methods.…”

Section: Introductionmentioning

confidence: 99%

Study of the Biotransformation of Benfluron Using the Isolated Perfused Rat Liver

Svoboda

Nobilis²,

Kvĕtina³

et al. 1999

Acta Med. (Hradec Kralove, Czech Repub.)

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The isolated perfused rat liver method (IPRL) was used to find, isolate and identify further metabolites of Phase I and Phase II biotransformation of the potential cytostatic agent benfluron with special regard to the conjugation processes. Its pharmacokinetic profile during the perfusion was also estimated. The rat liver was isolated from the body and perfused in vitro using a recirculating perfusion system. Benfluron was added to the reservoir as a bolus in doses of 200, 100, 30 mg/kg of body weigh and 1 mg/perfusate volume and also as a continual infusion in a dose of 0.1 mg/min in separate series of experiments. The following metabolites formed during Phase I biotransformation were found in the perfusion liquid as well as in the bile: benfluron N-oxide, 9-hydroxy benfluron, demethylated 9-hydroxy benfluron, demethylated benfluron, and reduced benfluron. The major Phase II metabolite found in the bile samples was the glucuronide of 9-hydroxy benfluron. The pharmacokinetic profile of benfluron in IPRL indicated its main disposition and metabolic pathway, i.e. its rapid extraction from perfusate by the liver (t1/2α = 3.76 min), 9-hydroxylation followed up O-glucuronidation and excretion to the bile. It was revealed that 12 % of the total dose of the parent compound was excreted to the bile in the form of conjugates during the first hour of perfusion, 32 % during 1.5 hour, and 70 % during 2 hours after the administration of benfluron. The conjugates with glucuronic acid represented 96-98 % of all metabolites found in the bile.

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Benfluron hydrochloride

Cited by 14 publications

References 0 publications

Exploring the HIV-1 Rev Recognition Element (RRE)–Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

Exploring the HIV-1 Rev Recognition Element (RRE)–Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

Disposition study of a new potential antineoplastic agent dimefluron in rats using high-performance liquid chromatography with ultraviolet and mass spectrometric detection

Study of the Biotransformation of Benfluron Using the Isolated Perfused Rat Liver

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