In-silico ANALYSIS OF 1,3-BIS (p-HYDROXYPHENYL)UREA AS ANTI-INFLAMMATORY THROUGH INHIBITION OF COX-1 AND TNF-α

Harahap, Urip; Purnomo, Hari; Satria, D.

doi:10.31788/rjc.2021.1436163

Cited by 9 publications

(8 citation statements)

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“…72 K3R interacts with TYR119 with pi-pi interaction, SER60 with hydrogen bond and other hydrophobic interactions with LEU57, and TYR59 residues of TNF-α dimer. 73 Hydrogen bond interaction was noted between the K3R and GLU202 and hydrophobic interaction with LEU164, ALA165, and HIS201 residue of MMP2. 74 K3R exhibited higher binding free energy (ΔG); -34.22, -57.35, -66.37, -48.20, and -57.85 with MMP9, TGF-β1, EGFR, TNF-α, and MMP2 respectively (Table 3).…”

Section: Molecular Dockingmentioning

confidence: 97%

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Byregowda,

Baby,

Maity

et al. 2024

F1000Res

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Background Idiopathic pulmonary fibrosis (IPF) is a disease with high mortality, and there are only two specific drugs available for therapeutic management with limitations. The study aims to identify comprehensive therapeutic mechanisms of Zingiber zerumbet rhizomes (ZZR) to treat IPF by using network pharmacology followed battery of in silico studies. Methods The protein-protein interaction network was developed using Cytoscape to obtain core disease targets involved in IPF and their interactive molecules of ZZR. Based on the pharmacophore properties of phytomolecules from ZZR, the drug targets in IPF were explored. Protein-protein interaction network was built in Cytoscape to screen potential targets and components of ZZR. Molecular docking and dynamics were conducted as an empirical study to investigate the mechanism explored through network pharmacology in relation to the hub targets. Results The network analysis conferred kaempferol derivatives that had demonstrated a promising therapeutic effect on the perturbed, robust network hubs of TGF-β1, EGFR, TNF-α, MMP2 & MMP9 reported to alter the biological process of mesenchymal transition, myofibroblast proliferation, and cellular matrix deposition in pulmonary fibrosis. The phytomolecules of ZZR act on two major significant pathways, namely the TGF-β-signaling pathway and the FOXO-signaling pathway, to inhibit IPF. Confirmational molecular docking and dynamics simulation studies possessed good stability and interactions of the protein-ligand complexes by RMSD, RMSF, rGyr, SASA, and principal component analysis (PCA). Validated molecular docking and dynamics simulations provided new insight into exploring the mechanism and multi-target effect of ZZR to treat pulmonary fibrosis by restoring the alveolar phenotype through cellular networking. Conclusions Network pharmacology and in silico studies confirm the multitargeted activity of ZZR in the treatment of IPF. Further in vitro and in vivo studies are to be conducted to validate these findings.

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Section: Molecular Dockingmentioning

confidence: 97%

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Byregowda,

Baby,

Maity

et al. 2024

F1000Res

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“…The hematological parameters tested for the acute toxicity of 1,3-bis(p-hydroxyphenyl) urea in rats include 1 : Hemoglobin (HB), 2 Hematocrit (HCT), 3 White Blood Cells (WBC), 4 Red Blood Cells (RBC), 5 Platelets, 6 Mean Corpuscular Volume (MCV), 7 Mean Corpuscular Hemoglobin (MCH), 8 Mean Corpuscular Hemoglobin Concentration (MCHC), 9 Eosinophils (EOS), 10 Monocytes (MON), and 11 Basophils (BAS). Using a One-Way Anova method and a Post Hoc Test (Tuckey HSD), the results showed that there was no significant difference between the control and treatment groups (p > 0.05), as HB, HCT, WBC, RBC, Thrombo, MCV, MCH, MCHC, EOS, MON, and BAS = 0.412, 0.633, 0.894, urea did not affect the hematological values between the control and treatment groups.…”

Section: Hematological Parametersmentioning

confidence: 99%

“…This indicated that the compound had the potential of being developed as an anti-inflammatory agent. 6 The anti-inflammatory action of non-steroidal drugs is mainly the inhibition of prostaglandin synthesis by cyclooxygenase-2 (COX-2). This is involved in the production of prostaglandins during the processes of inflammation.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity and toxicity evaluation of 1,3-bis(p-hydroxyphenyl)urea

Waruwu

Harahap²,

Yuandani³

et al. 2022

F1000Res

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Background: Inflammation is a normal protective response caused by tissue damage through physical trauma, chemical damage, or invasion of pathogenic microorganisms. 1,3-bis(p-hydroxyphenyl)urea is a modified p-aminophenol compound, which is considered to have strong analgesic activity based on cyclooxygenase-2 inhibition and has fewer hepatotoxic side effects. In-silico test showed 1,3-bis(p-hydroxyphenyl)urea has COX-1 and TNF- binding activity, so it has the potential to be developed as an anti-inflammatory agent. Anti-inflammatory activity was tested using mice. Toxicity test was conducted to test the safety of 1,3-bis(p-hydroxyphenyl)urea. Methods: Anti-inflammatory test was carried out by measuring the percentage of inflammation in rat paws using a plethysmometer after administration of 1,3-bis(p-hydroxyphenyl)urea induced by carrageenan 1%, and then histology was performed to observe the number of neutrophils. A toxicity test using OECD guidelines carried out acute toxicity for 24 hours and was observed for 14 days. The subchronic toxicity test was carried out for 28 days, followed by 42 days in the satellite group. Results: Analysis of rat paw inflammation volume showed 1,3-bis(p-hydroxyphenyl)urea could suppress inflammation after carrageenan-1% induction. The group given {1.3 bis (p-Hydroxyphenyl)urea} and sodium diclofenac 2.25 mg/kg BW had a significant difference in results (p<0.05) with 0.5% Na CMC group. Doses of 50, 100, and 200 mg/kg BW showed no significant difference (p>0.05) with diclofenac sodium. The number of neutrophils also decreased compared to the 0.5% Na CMC group. The acute toxicity test of 1,3-bis(p-hydroxyphenyl)urea did not cause toxic symptoms and death up to a dose of 5000 mg/kg BW. The microscopic results of subchronic toxicity of liver tissue experienced hydropic degeneration at a dose of 1000 mg/kg BW; in the lungs causes congestion, and microscopic renal tissue undergoes Bowman space dilatation and tubular lumen dilatation, but this condition is reversible. Conclusion: This 1,3-bis(p-hydroxyphenyl)urea compound had an anti-inflammatory activity and relatively low toxicity.

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“…In vivo test results proved that the compound {1,3 bis (p-Hydroxyphenyl)urea} had potential as an analgesic based on the inhibition of the cyclooxygenase (COX-2) enzyme [7], whereas in silico tests on COX-1 and TNF-α showed that {1,3 bis (p-Hydroxyphenyl)urea} had higher activity in binding COX-1 (1CQE) and TNF-α (2AZ5) than the control, dexamethasone and diclofenac. This compound has the potential to be developed as an anti-inflammatory agent [8,9]. The compound {1,3 bis (p-Hydroxyphenyl)urea} has anti-inflammatory activity by reducing the percentage of inflammation, the number of neutrophils and the amount of expression of COX-2, TNFα, IL-1β and IL-6 [10,11].…”

Section: Introductionmentioning

confidence: 99%

Toxic Effect Of The Compound {1,3 Bis (P-Hydroxyphenyl) Urea} On Triiodothyronine (T3) Hormone Levels In Pregnant White Rats (Rattus Norvegicus L.)

Fauzi

Harahap

Yuandani

et al. 2023

International Journal of Science, Technology & Management

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Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs for pregnant women to treat fever, pain and inflammation. Specific NSAIDs can displace thyroid hormone from its protein binding sites, causing thyroid hormone measurement problems. {1,3 bis (p-Hydroxyphenyl)urea} is a modified p-aminophenol compound with potent analgesic and anti-inflammatory activity and less toxicity. This study is a follow-up to previous research to observe the toxic effect on triiodothyronine hormone levels after administration of {1,3 bis(p-Hydroxyphenyl)urea} compound in pregnant white rats. The toxic effect test was carried out by giving the test preparation to pregnant rats, which had been divided into five groups, namely the normal control group (CMC-Na 0.5%), the positive control (Gabapentin 50 mg/kg BW), Compound {1.3 bis (p- Hydroxyphenyl)urea} at a dose of 50 mg/kg BW, 500 mg/kg BW and 1000 mg/kg BW. Mice were given the test preparation every day from the 6th to the 15th day of pregnancy. Blood was taken on the 16th day, and T3 hormone levels were measured using the ELISA method. The results showed that the T3 hormone levels in the {1,3 bis(p-Hydroxyphenyl)urea group had no significant difference from the normal control group, so it was concluded that {1,3 bis(p-Hydroxyphenyl)urea) did not have a significant effect on the hormone T3.

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In-silico ANALYSIS OF 1,3-BIS (p-HYDROXYPHENYL)UREA AS ANTI-INFLAMMATORY THROUGH INHIBITION OF COX-1 AND TNF-α

Cited by 9 publications

References 0 publications

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Anti-inflammatory activity and toxicity evaluation of 1,3-bis(p-hydroxyphenyl)urea

Toxic Effect Of The Compound {1,3 Bis (P-Hydroxyphenyl) Urea} On Triiodothyronine (T3) Hormone Levels In Pregnant White Rats (Rattus Norvegicus L.)

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