Synthesis, anti-inflammatory, cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide, oxime, and β-phenylalanine scaffolds: a molecular docking study

Abdel‐Aziz, Alaa A.‐M.; El‐Azab, Adel S.; Alsaif, Nawaf A.; Alanazi, Mohammed M.; El-Gendy, Manal A.; Obaidullah, Ahmad J.; Alkahtani, Hamad M.; Almehizia, Abdulrahman A.; Al-Suwaidan, Ibrahim A.

doi:10.1080/14756366.2020.1722120

Cited by 20 publications

(17 citation statements)

References 23 publications

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“…The imide core is also present in compounds whose activity is related to CNS activity [ 32 , 33 , 34 , 35 , 36 ]. In particular, much attention has been paid to their ability to inhibit cyclooxygenases, anti-inflammatory, and analgetic activity [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. To date, several drugs with cyclic imide structure have been approved, including lurasidone, buspirone, ethosuximide, mesuximide, and the IMiDs class includes thalidomide and its analogues lenalidomide, pomalidomide, apremilast ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Redzicka

Czyżnikowska

Wiatrak

et al. 2021

IJMS

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In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The structural properties of the compounds were characterized by 1H NMR, 13C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 2h. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Redzicka

Czyżnikowska

Wiatrak

et al. 2021

IJMS

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“…The inhibitory effect of 12r on iNOS and COX‐2 expression was confirmed (Figure 5f). Moreover, there was no apparent inhibition of COX‐1 expression (Abdel‐Aziz et al., 2020). Overall, these results indicated that compound 12r exerted an inhibitory effect on the activation of NF‐κB and related pro‐inflammatory mediators.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and anti‐inflammatory study of novel N‐heterocyclic substituted Aloe‐emodin derivatives

Qiu

Pei

et al. 2020

Chem Biol Drug Des

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A novel series of Aloe‐emodin derivatives containing N‐heterocyclic moieties was designed and synthesized. The structure‐activity relationship studies (SARs) indicated that the replacement of hydroxyethyl and benzhydryl piperazine groups could improve efficacy. Compounds 12r and 14a–14c exhibited a higher inhibitory effect on LPS‐induced nitric oxide (NO) production in RAW264.7 macrophages than Aloe‐emodin did. Among them, 12r showed the most potent inhibition with an IC50 value of 5.66 ± 0.47 μM. Further toxicity and pharmacokinetic studies were carried out and 12r was found to be the most active structure with low toxicity risk and good metabolic properties. It could also decrease the levels of IL‐1β, TNF‐α, PGE2 and inhibit the activation of nuclear factor‐κB signalling pathway. Importantly, 12r showed oral bioavailability of up to 55.16% and attenuated the inflammatory symptoms in an ulcerative colitis mouse model in vivo. These results indicate that 12r is suitable for development as an anti‐inflammatory agent.

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“…Two chemical entities appear with weighing importance in the OPLS-DA model, 2-Methylpropanoyl phosphate and 1,3-Benzenedisulfonamide; however, neither of them has been previously reported in the human metabolome. Interestingly, compounds containing the sulphonamide moiety present potential biological activities, such as carbonic anhydrase and COX-1/2 inhibition, as well as anti-inflammatory, and antitumor activities [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic changes during exclusive enteral nutrition in pediatric Crohn’s disease patients

et al. 2022

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Background and aims Exclusive enteral nutrition is recommended as a first-line treatment in active pediatric Crohn’s Disease, but its mechanism of action is still not clear. We aimed to assess alterations in the metabolic profile of newly diagnosed pediatric Crohn’s Disease patients before and during exclusive enteral nutrition therapy. Methods Plasma samples from 14 pediatric Crohn’s Disease patients before and after 3–4 weeks on exclusive enteral nutrition were analyzed using mass spectrometry. T-test, fold change and orthogonal partial least squares discriminant analysis were used for mining significant features. Correlation analysis was performed between the annotated features and the weighted pediatric Crohn’s disease activity index using Pearson r distance. Results Among the 13 compounds which decreased during exclusive enteral nutrition, most are related to diet, while one is a bacterial metabolite, Bacteriohopane-32,33,34,35-tetrol. The phosphatidic acid metabolite PA(15:1/18:0) was significantly reduced and correlated with the weighted pediatric Crohn’s disease activity index. Lipids increased during exclusive enteral nutrition therapy included phosphatidylethanolamines; PE(24:1/24:1), PE(17:2/20:2) and one lactosylceramide; LacCer(d18:1/14:0). Conclusion Food additives and other phytochemicals were the major metabolites, which decreased following the exclusion of a regular diet during exclusive enteral nutrition. An alteration in bacterial biomarkers may reflect changes in intestinal microbiota composition and metabolism. Thus, metabolomics provides an opportunity to characterize the molecular mechanisms of dietary factors triggering Crohn’s Disease activity, and the mechanisms of action of exclusive enteral nutrition, thereby providing the basis for the development and evaluation of improved intervention strategies for prevention and treatment.

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Synthesis, anti-inflammatory, cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide, oxime, and β-phenylalanine scaffolds: a molecular docking study

Cited by 20 publications

References 23 publications

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Design, synthesis and anti‐inflammatory study of novel N‐heterocyclic substituted Aloe‐emodin derivatives

Metabolic changes during exclusive enteral nutrition in pediatric Crohn’s disease patients

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