High-performance liquid chromatography analysis of Bobel-24 in biological samples for pharmacokinetic, metabolic and tissue distribution studies

Garcı́a-Capdevila, L; López-Calull, C; Pompermayer, S; Arroyo, Carmen M.; Molins-Pujol, A. M.; Bonal, Joaquin

doi:10.1016/s0378-4347(97)00645-2

Cited by 7 publications

(7 citation statements)

References 4 publications

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“…As Bobel-24 was originally introduced and described as a COX and LOX inhibitor (31,33), we asked whether these inhibitions were responsible for the cytotoxic activity. We analyzed whether Bobels interfered with the arachidonic acid metabolism by analyzing metabolites of arachidonic acid in K562 (myeloid cell line) and Raji (lymphoid cell line).…”

Section: Bobel-16 and Bobel-4 Cause The Lowest Survival On Leukemia Cmentioning

confidence: 99%

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Parreño

Vaqué²,

Casanova³

et al. 2006

Molecular Cancer Therapeutics

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Abstract2,4,6-Triiodophenol (Bobel-24, AM-24) was originally described as a nonsteroid antiinflammatory molecule. We have synthesized three derivatives of and tested their activities as putative antileukemic agents. We have found that Bobel-24 and Bobel-16 were dual inhibitors of cyclooxygenase and 5-lipoxygenase, whereas Bobel-4 and Bobel-30 were selective against 5-lipoxygenase. We have tested the antiproliferative activity of these compounds on a panel of cell lines derived from myeloid and lymphoid leukemias (K562, Raji, HL-60, and Molt4). The cytotoxic IC 50 in these cell lines ranged between 14 and 50 Mmol/L, but it was higher for nontransformed cells such as 32D, NIH3T3, or human leukocytes. All compounds showed cytotoxic activity on all tested cell lines, accompanied by DNA synthesis inhibition and arrest in the G 0 /G 1 phase. Bobel-16, Bobel-4, and Bobel-24 induced a caspase-independent cell death in K562 and Raji cells, accompanied by chromatin condensation, cytochrome c release, and dissipation of mitochondrial membrane potential in a concentration-dependent manner and production of reactive oxygen species. As the proto-oncogene MYC is involved in mitochondrial biogenesis and survival of leukemia cells, we tested its effect on bobel activity. Bobel-24 induced down-regulation of MYC in K562 and, consistently, ectopic expression of MYC results in partial protection towards the cytotoxic effect of Bobel-24. In conclusion, Bobel derivatives induce a caspase-and Bcl-2-independent cell death in which mitochondrial permeabilization and MYC down-regulation are involved. Bobels may serve as prototypes for the development of new agents for the therapy of leukemia. [Mol Cancer Ther 2006;5(5):1166-75]

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Section: Bobel-16 and Bobel-4 Cause The Lowest Survival On Leukemia Cmentioning

confidence: 99%

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Parreño

Vaqué²,

Casanova³

et al. 2006

Molecular Cancer Therapeutics

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“…[10][11][12] Some iodinated compounds have found application in the pharmaceutical field and recently a new drug based on 2,4,6-triiodophenol (2,4,6-triiodophenol or Bobel-24) has been proposed as an anti-inflammatory. 13 This compound has been shown to possess anti-inflammatory properties through in vivo tests in different animal models. Some interesting properties have been described for phenolic compounds.…”

Section: Introductionmentioning

confidence: 99%

“…It has been found that 2,4,6-triiodophenol is a 5-lipoxygenase inhibitor, which could be effective in the therapy of inflammatory diseases mediated by leukotrienes. 13 Presently, studies are being carried out to demonstrate Bobel-24 is effective in the treatment of articular diseases and seborrheic dermatitis in dogs. 13 The development of such studies requires not only a reliable and fast analytical method but also a sensitive technique capable of determining 2,4,6-triiodophenol and its possible metabolites and degradation products in different types of biological samples.…”

Section: Introductionmentioning

confidence: 99%

Determination of 2,4,6-triiodophenol and its metabolites in human urine by anion-exchange chromatography with ICP-MS detection

Wuilloud

Selar

Kannamkumarath

et al. 2004

J. Anal. At. Spectrom.

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An analytical method using high-performance liquid chromatography (HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) was developed for the separation and determination of iodophenol compounds in human urine samples. The advantages of using highly-sensitive 127 I detection provided by ICP-MS for the speciation of 2,4,6-triiodophenol, 4-iodophenol and 2-iodophenol are shown in this work. 2,4,6-triiodophenol is also referred to as Bobel-24, an anti-inflammatory. Chromatographic conditions were optimized using UV absorption at 254 nm and ICP-MS detection of 127 I and a comparative study between these two detection systems was developed. The separation of iodophenol species was studied by two different chromatographic modes: reversed-phase and anion-exchange chromatography. Complete chromatographic resolution of the iodophenol species was obtained in 100% aqueous phase solution using gradient elution of NaOH (50 mmol l À1 ) and NaOH (50 mmol l À1 ) with hexadecyltrimethylammonium bromide (CTAB). Total resolution was obtained in a minimal retention time of 7 min. Since the separation of the iodophenol species was performed in an aqueous mobile phase, high sensitivity was obtained with the ICP-MS instrument. The detection limits obtained were between 0.08-0.22 mg l À1 as iodophenol compounds. On the other hand, the detection limits obtained with UV detection were 300-325 times higher with ICP-MS. Finally, the analytical methodology was applied for the determination of iodophenols in human urine.

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“…Bobel-24 is a nonsteroidal antiinflammatory compound ( Fig. 1) (6,10,11). It is under clinical development as a potent leukotriene B 4 synthesis inhibitor (17).…”

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confidence: 99%

Bobel-24 Activity against Cryptosporidium parvum in Cell Culture and in a SCID Mouse Model

Rueda

Fenoy

Simón

et al. 2008

Antimicrob Agents Chemother

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The anticryptosporidial activity of Bobel-24 (2,4,6-triiodophenol) was studied for the first time, resulting in a reduction of the in vitro growth of Cryptosporidium of up to 99.6%. In a SCID mouse model of chronic cryptosporidiosis, significant differences (P < 0.05) in oocyst shedding were observed in animals treated with 125 mg/kg/day. These results merit further investigation of Bobel-24 as a chemotherapeutic option for cryptosporidiosis.Cryptosporidium parvum is considered one of the top four causes of self-limiting diarrhea in humans and in several animal species (15). In immunocompromised individuals, cryptosporidial infection may become chronic and life threatening because no completely effective treatment is available (7).The molecular mechanism involved in the initial interaction between C. parvum sporozoites and epithelial cells is still unclear. One of the mechanisms of C. parvum attachment is the interaction between galactose-N-acetylgalactosamine (Gal/ GalNAc) epitopes on the epithelial apical membrane and Gal/ GalNAc-specific sporozoite surface lectins (3). Invasion by and intracellular development of the parasite lead to the destruction of epithelial cells, resulting in blunting of intestinal villi, crypt hyperplasia, and cytoskeletal remodeling. In addition, there are decreased sodium absorption, epithelial chemokine production, and increased prostaglandin production (16), which are directly related to the notable inflammatory response that follows Cryptosporidium infection and characterizes its pathology (9).To further the improvement of treatment against cryptosporidiosis, we studied the anticryptosporidial activity of 4,. This compound is able to inhibit lectin expression (11). In addition, Bobel-24 is considered a dual inhibitor of lipoxygenase and cyclooxygenase, which are involved in the resolution of inflammatory diseases (10, 13).The C. parvum IOWA bovine isolate used for this study was kindly provided by M. J. Arrowood (Centers for Disease Control and Prevention, Atlanta, GA). Bobel-24 is a nonsteroidal antiinflammatory compound (Fig. 1) (6, 10, 11). It is under clinical development as a potent leukotriene B 4 synthesis inhibitor (17). For in vitro studies, Bobel-24, used as a pure compound (purity of 99.6%, obtained from Chemical Iberica SL, Salamanca, Spain), was first dissolved in dimethyl sulfoxide (DMSO) and then diluted with phosphate-buffered saline. In an MTT cytotoxicity assay (5), viability percentages (Ͼ95%) of HCT-8 cells with Bobel-24 concentrations lower than 100 M were observed. To study in vitro activity of Bobel-24, 8 ϫ 10 5 excysted oocysts/ml (1) were inoculated in confluent HCT-8 cell monolayers as previously described (2). To assess the effect on sporozoite attachment to HCT-8 cells, we incubated sporozoite suspensions with Bobel-24 (90 M) before use, we incubated HCT-8 cells with Bobel-24 (90 M) before infection, and to evaluate the effect of Bobel-24 on C. parvum development in HCT-8, we incubated infected cells afterwards with 90 M Bobel-24 for 48 h. Paromomycin ...

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High-performance liquid chromatography analysis of Bobel-24 in biological samples for pharmacokinetic, metabolic and tissue distribution studies

Cited by 7 publications

References 4 publications

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Determination of 2,4,6-triiodophenol and its metabolites in human urine by anion-exchange chromatography with ICP-MS detection

Bobel-24 Activity against Cryptosporidium parvum in Cell Culture and in a SCID Mouse Model

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