Design, synthesis, biological evaluation and docking studies of new 3-(4,5-dihydro-1 H -pyrazol/isoxazol-5-yl)-2-phenyl-1 H -indole derivatives as potent antioxidants and 15-lipoxygenase inhibitors

Elbordiny, Haydi S.; El-Miligy, Mostafa M.M.; Kassab, Shaymaa E.; Daabees, Hoda G.; Ali, Waleed A.M.; El-Hawash, Soad A.M.

doi:10.1016/j.ejmech.2018.01.026

Cited by 46 publications

(13 citation statements)

References 41 publications

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“…Such analyses involved the inspection of intermolecular interactions with the most relevant amino acid residues involved in ligand binding, both directly or through the use of water molecules, and coordination (or not) with Fe 3+ ion at the active site of 15-LOX-2. 31,32 In this regard, the LOX-conandroside complex displayed a slightly higher docking score (92.7) than the observed for quercetin (71.5). Analysis of the interaction pattern for conandroside (Figure 3b) highlighted the existence of hydrogen bonds among one of the hydroxyl groups at catecholic ether moiety with His 373 and Ile 676 , and also the coordination of this group with Fe 3+ ion at the active site, which are considered pivotal interactions for enzyme inhibition and for the subsequent interference in the redox cycle of 15-LOX-2.…”

Section: Resultsmentioning

confidence: 81%

Isolation, in vitro and in silico Evaluation of Phenylethanoid Glycoside from Arrabidaea brachypoda as Lipoxygenase Inhibitor

Bertanha

Gimenez

Furtado

et al. 2020

J. Braz. Chem. Soc.

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Lipoxygenase (LOX) plays an important role in inflammatory processes and Arrabidaea brachypoda (DC.) Bureau (Bignoniaceae) has been described as presenting antiinflammatory activity. Therefore, the objective of this study was to develop a high-performance liquid chromatography (HPLC) procedure to directly recognize LOX inhibitor compounds in A. brachypoda crude extract, facilitating the isolation, characterization of bioactive compounds, evaluation of natural compounds using an in vitro 15-LOX assay and prediction of the most probable binding modes of their main constituent through molecular docking simulations. The chemical analysis was performed by ethanol crude extract microfractionation using HPLC-DAD (diode array detector) associated to a fraction collector. The bioactive chromatogram displayed a peak with 50.9% LOX inhibition at 13.6 min retention time. The extract was purified and conandroside was isolated, presenting a LOX inhibitory activity with an inhibitory concentration (IC 50) of 7.8 ± 1.1 µM, close to standard quercetin (IC 50 7.6 ± 0.3 µM). Additionally, conandroside was not cytotoxic to normal cells (GM07492A). The LOX-conandroside complex displayed a slightly higher docking score (92.7) than quercetin (71.5). These results together suggest that conandroside could be explored as lipoxygenase inhibitor.

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Section: Resultsmentioning

confidence: 81%

Isolation, in vitro and in silico Evaluation of Phenylethanoid Glycoside from Arrabidaea brachypoda as Lipoxygenase Inhibitor

Bertanha

Gimenez

Furtado

et al. 2020

J. Braz. Chem. Soc.

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“…Moreover, LOX products, leukotrienes, and lipoxins, have a part in significant metabolic functions such as organelle degradation (25), transcription regulation (26), and possibly tumor cell metastasis (27). Therefore, the inhibition of LOXs is considered an important target for the treatment of LOX-related diseases (5)(6)(7)16,(28)(29)(30)(31)(32)(33)(34)(35). There are some reports which show the results of LOX inhibition studies in the literature.…”

Section: Introductionmentioning

confidence: 99%

Can soybean lipoxygenases be real models for mammalian lipoxygenases? A bioinformatics approach

Cengiz

Çavaş

2021

Journal of the Turkish Chemical Society Section A: Chemistry

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Soybean lipoxygenase-1 is one of well-studied enzymes because it is considered as a model enzyme for mammalian lipoxygenases. In general, the soybean lipoxygenase-1 is used in the test of inhibitory activities of various compounds. The present study provides a bioinformatics approach for comparison of various lipoxygenases in the databases. Their various physical and chemical parameters such as molecular weight, theoretical pI, amino acid composition, aliphatic index, and grand average of hydropathicity and the multiple sequence alignments of the lipoxygenases were computed by using several bioinformatics tools. In order to see phylogenetic relationships among lipoxygenases, a phylogenetic tree was constructed. The first three most abundant amino acids in soybean lipoxygenase-1 and 15-lipoxygenase (human) are L (10.3 %), S (7.4 %), A (6.7 %) and L (13.3 %), G (7.4 %), V (7.1 %), respectively. According to the phylogenetic tree, the soybean lipoxygenases are within separate clade compared to the mammalian lipoxygenases. In conclusion, soybean lipoxygenase-1 may not fully characterize the human lipoxygenase-15 since there are remarkable sequence-based differences, which are obtained by using bioinformatics tools between soybean lipoxygenase-1 and lipoxygenases from other sources especially from human. In this context, the researchers, who are aware of the problems described above and who have similar concerns, have begun to use recombinant DNA technology to produce recombinant human lipoxygenase-15 enzyme.

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“…[13][14][15]. 4,5-Dihydro-1H-pyrazole derivatives have luminescent properties [16] and also exhibit antibacterial [17], antioxidant [18], analgesic [19], anti-in ammatory [20], and antimycobacterial activity [21]. It should be noted that the pyridine-containing derivatives of 4,5-dihydro-1H-pyrazole have low toxicity, as well as their phenyl-substituted analogs.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4,5-dihydro-1H-pyrazole derivatives based on 3-acetyl-5-nitropyridines

et al. 2021

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Design, synthesis, biological evaluation and docking studies of new 3-(4,5-dihydro-1 H -pyrazol/isoxazol-5-yl)-2-phenyl-1 H -indole derivatives as potent antioxidants and 15-lipoxygenase inhibitors

Cited by 46 publications

References 41 publications

Isolation, in vitro and in silico Evaluation of Phenylethanoid Glycoside from Arrabidaea brachypoda as Lipoxygenase Inhibitor

Isolation, in vitro and in silico Evaluation of Phenylethanoid Glycoside from Arrabidaea brachypoda as Lipoxygenase Inhibitor

Can soybean lipoxygenases be real models for mammalian lipoxygenases? A bioinformatics approach

Synthesis of 4,5-dihydro-1H-pyrazole derivatives based on 3-acetyl-5-nitropyridines

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