Synthesis and 5-lipoxygenase inhibitory activities of eicosanoid compounds

Arai, Yoshinobu; Shimoji, Katsuichi; Konno, Mitoshi; Konishi, Yoshitaka; Okuyama, Shigehiro; Iguchi, Sadahiko; Hayashi, Masaki; Miyamoto, Tsumoru; Toda, Masaaki

doi:10.1021/jm00355a015

Cited by 45 publications

(9 citation statements)

References 4 publications

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“…Furthermore, when nonspecific effects and leukotriene receptor antagonist activity are excluded, the effects of active compounds may be largely attributable to an effect directly or indirectly [30][31][32] at 5-LO.…”

Section: Discussionmentioning

confidence: 99%

Antagonism of Antigen-Induced Contraction of Isolated Guinea-Pig Trachea by 5-Lipoxygenase Inhibitors

Hand¹,

Schwalm²,

Lewis³

1986

Int Arch Allergy Immunol

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Tracheal strips were obtained from guinea pigs actively sensitized to chicken ovaibumin (OA). OA-induced contractile responses, obtained by cumulative log addition, were found to be comparable both temporally and in magnitude with responses obtained by single addition of OA. The concentration-response curve obtained by cumulative addition of OA was partially inhibited by pretreatment of tissues with chlorpheniramine. On tracheal spirals treated with chlorpheniramine, indomethacin enhanced OA-induced contractile responses. In the presence of chlorpheniramine and indomethacin, pretreatment with one of the reference 5-lipoxygenase inhibitors (ETYA, NDGA, phenidone or BW-755C) both reduced the maximum contractile response and produced a rightward shift of the OA concentration-response curve. The data suggest that cumulative log addition of OA, on the indomethacin- and chlorpheniramine-treated guinea-pig trachea, is a useful model for evaluating compounds active as either inhibitors of 5-lipoxygenase or antagonists of the products of this pathway.

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Section: Discussionmentioning

confidence: 99%

Antagonism of Antigen-Induced Contraction of Isolated Guinea-Pig Trachea by 5-Lipoxygenase Inhibitors

Hand¹,

Schwalm²,

Lewis³

1986

Int Arch Allergy Immunol

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“…Polyacetylenes as arachidonic acid mimetics Short after the discovery of the 5-LO enzyme, various AA derivatives, in particular those with acetylene moieties such as 5,8,11,14-eicosatetraynoic acid (ETYA) [65] and 5,8,11-eicosatriynoic acid [188], but also 15-hydro(pero)xy-5,8,11,13-eicosatetraenoic acid (15-H(P)ETE) [189,190], 5,12-diHETE, or LT-analogues like 5,6-methano-LTA 4 [191], [192] were found to inhibit 5-LO activity. Moreover, AA-861 1 [2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, see above] contains two acetylene moieties in addition to the redox-active 1,4-benzoquinone structure [67].…”

Section: Alkaloidsmentioning

confidence: 99%

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Werz¹

2007

Planta Med

151

135

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4 , D 4 and E 4 . LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structureactivity relationships are discussed.

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“…The compounds identified under LC-MS in this study were mostly non-volatile and could not have been identified by GC-MS. The novel fatty acid is quite interesting and cyclopropane fatty acids (CFA) have been isolated from several sources such as millipedes (Oudejans, 1971), molluscs (Fenical et al, 1979), molds (Saito and Ochiai, 1998) and a lot of them have been synthesized (Shah et al, 2014, Arai et al, 1983. CFAs are typically found in microorganisms, seed oils of subtropical plants, protozoa and less commonly, within fats and phospholipids produced by animals.…”

Section: Resultsmentioning

confidence: 99%

LC-MS analysis of oils of Monodora myristica and Monodora tenuifolia and isolation of a novel cyclopropane fatty acid

Al‐Tannak

Khadra

Igoli

et al. 2019

Natural Product Research

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Seeds of Monodora myristica and M. tenuifolia were extracted with hexane and the extracts were subjected to column chromatography, LC-MS and NMR analysis. In addition to masses of previously isolated compounds, other masses corresponding to unidentified compounds from the plants were detected. Using 2D NMR techniques, one of the fractions from M. tenuifolia was characterised as a novel 13-(2-butylcyclopropyl)-6,9-dodecadienoic acid. However, none of the compounds detected in LC-MS corresponded to the ones previously identified by GC-MS.

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Synthesis and 5-lipoxygenase inhibitory activities of eicosanoid compounds

Cited by 45 publications

References 4 publications

Antagonism of Antigen-Induced Contraction of Isolated Guinea-Pig Trachea by 5-Lipoxygenase Inhibitors

Antagonism of Antigen-Induced Contraction of Isolated Guinea-Pig Trachea by 5-Lipoxygenase Inhibitors

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

LC-MS analysis of oils of Monodora myristica and Monodora tenuifolia and isolation of a novel cyclopropane fatty acid

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