Inhibition of Leukotriene Production by N-(4-(4-(Diphenylmethyl)-1-piperazinyl)butyl)-3-(6-methyl-3-pyridyl) Acrylamide (AL-3264), a New Antiallergic Agent.

Ishii, Katsumi; Yakuo, Ikuhisa; Motoyoshi, Satoru; Nakagawa, Hiroyo; Nakamura, Hideo

doi:10.1254/jjp.65.19

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…Numerous in vitro studies indicate that a wide range of phenolic compounds might exert anti-inflammatory effects by targeting the 5-LOX pathway ( Table S1 ). Thus, caffeic acid, hydroxytyrosol, resveratrol, curcumin, NDGA and quercetin are compounds with the capacity to reduce the formation of 5-HETE, LTB 4 (and its ω-oxidized metabolites), and Cys-LTs [ 107 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. Although desirable, these effects should be considered with caution since inhibition of the 5-LOX pathway could result in higher (pro-inflammatory) COX-2 metabolite levels by shunting the substrate, AA.…”

Section: Resultsmentioning

confidence: 99%

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Giménez‐Bastida

González‐Sarrías

Llopis

et al. 2021

IJMS

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5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammatory cytokines (TNF-α, IL-1β), prostaglandins (PGE2), and the interaction with NF-κB and cyclooxygenase 2 (COX-2) pathways. Much less is known about the 5-lipoxygenase (5-LOX) pathway as a target of dietary (poly)phenols. This systematic review aimed to summarize how dietary (poly)phenols target the 5-LOX pathway in preclinical and human studies. The number of studies identified is low (5, 24, and 127 human, animal, and cellular studies, respectively) compared to the thousands of studies focusing on the COX-2 pathway. Some (poly)phenolics such as caffeic acid, hydroxytyrosol, resveratrol, curcumin, nordihydroguaiaretic acid (NDGA), and quercetin have been reported to reduce the formation of 5-LOX eicosanoids in vitro. However, the in vivo evidence is inconclusive because of the low number of studies and the difficulty of attributing effects to (poly)phenols. Therefore, increasing the number of studies targeting the 5-LOX pathway would largely expand our knowledge on the anti-inflammatory mechanisms of (poly)phenols.

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Section: Resultsmentioning

confidence: 99%

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Giménez‐Bastida

González‐Sarrías

Llopis

et al. 2021

IJMS

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“…Traditionally symptomatic treatment of allergies and bronchial asthma has been provided by β-sympathomimetic agents, methylxanthines, corticosteroids, and anticholinergics [1][2][3]. Japanese authors have synthesized a series of acrylamide derivatives linked with different piperazines via alkyl chains and proved them as promising anti-allergic candidates (Figure 1(A)) [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some <i>N</i>-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents

El-Salam¹,

Shalaby²,

El-Sawy³

et al. 2013

OJSTA

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An interesting approach for the design of anti-allergies is rationally considered. It was proved that current anti-allergic drugs comprise piperazine and acrylic acid segments. In harmony with these findings, new products 5a-u were synthesized starting from conjugated 2-thiopheneacrylic acid with amino acid esters 3a-g followed by coupling of their acid derivatives 4a-g with some piperazine segments, with the aim to increase their biological activities and decrease side effects. The anti-allergic and anti-inflammatory activities of the products were evaluated and promising results were obtained.

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Inhibitory Effect of AL-3264, a New Antiallergic Agent, on the Prausnitz-Küstner Reaction and Leukotriene Production in Monkeys

Yakuo¹,

Ishii²,

Sakaki³

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-To clarify the antiallergic effect and antiallergic mechanism of -1-piperazinyl]butyl]-3-(6-methyl-3-pyridyl)acrylamide) in monkeys, its effects on the Prausnitz-Kustner (P-K) reaction, the histamine skin reaction and leukotriene production were examined. In contrast to ketotifen and mepyramine, AL-3264 inhibited the P-K reaction, which is mainly mediated by leukotriene and histamine, more clearly than the skin reaction evoked by histamine alone. AL-3264 also inhibited the leukotriene (LT) production in the broncho-alveolar cells, suggesting that the inhibition of LT production actually contributes to the antiallergic effect of AL-3264.Keywords: AL-3264, Prausnitz-Kustner reaction, Monkey(AL-3264) is a new antiallergic agent that possesses a 5-lipoxygenase (5-LO) inhibiting property together with the abilities to block histamine HI-receptors and inhibit histamine release (1), but has very little sedative effect (2). The metabolism of AL-3264 in humans has also been assessed to be similar to that in monkeys, but not in rats.The monkey is thought to be a good experimental animal in which to develop allergic reactions, i.e., asthma, cedar pollinosis and the Prausnitz-Kustner (P-K) reaction (3 -5), because its mast cells and basophils can be passively sensitized with human IgE antibody (6, 7). We recently revealed that the P-K reaction in monkeys is mediated by leukotriene (LT) and histamine, similar to the mediation of human allergic diseases, and proposed that it is useful for the evaluation of antiallergic drugs (unpublished data, I. Yakuo and H. Nakamura).Some antiallergic drugs with multiple mechanisms of action have been developed, but these in vivo mechanisms of action have hardly been compared at the same time and at the effective dose. To assess the antiallergic effect and antiallergic mechanism of AL-3264 in monkeys, the effect of AL-3264 on the P-K reaction was compared with that on the histamine skin reaction in the same monkeys.Furthermore, its effect on LT production was examined using the broncho-alveolar cells of monkeys pretreated with AL-3264. Broncho-alveolar lavage is a useful method for the collection of proinflammatory cells and for the diagnosis or treatment of respiratory diseases. The method that is generally used in clinical studies is applied to experimental animals such as monkeys. Young adult cynomolgus monkeys (Japan SLC, Inc., Hamamatsu) were used for the experiments at an interval of more than a month. The P-K reaction was performed as follows: Forearm skin sites of monkeys (female, 2.5-4 kg) were sensitized with an intradermal injection (20 p1/site) of 5 times-diluted serum from an asthmatic patient. Two days later, the monkeys were challenged with dust mite antigen extract by an intradermal injection (0.2 pg/20 pl/site) into the 6 sensitized skin sites. In the same monkeys, the histamine skin reaction was also induced by an intradermal injection of histamine solution (0.2 pg/20 pl/site) into 5 unsensitized forearm skin sites. After 20 min (antigen injection) or 10 min (hist...

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Inhibition of Leukotriene Production by N-(4-(4-(Diphenylmethyl)-1-piperazinyl)butyl)-3-(6-methyl-3-pyridyl) Acrylamide (AL-3264), a New Antiallergic Agent.

Cited by 3 publications

References 22 publications

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Synthesis of Some <i>N</i>-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents

Inhibitory Effect of AL-3264, a New Antiallergic Agent, on the Prausnitz-Küstner Reaction and Leukotriene Production in Monkeys

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Inhibition of Leukotriene Production by N-(4-(4-(Diphenylmethyl)-1-piperazinyl)butyl)-3-(6-methyl-3-pyridyl) Acrylamide (AL-3264), a New Antiallergic Agent.

Cited by 3 publications

References 22 publications

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Synthesis of Some &lt;i&gt;N&lt;/i&gt;-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents

Inhibitory Effect of AL-3264, a New Antiallergic Agent, on the Prausnitz-Küstner Reaction and Leukotriene Production in Monkeys

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Synthesis of Some <i>N</i>-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents