Synthesis of novel 1,2,3-triazole based benzoxazolinones: Their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation
“…8 ). The similar types of molecular docking were reported earlier to understand the probable interactions between TNF-α protein and IC [ 39 , 40 ]. Fig.…”
BackgroundThe root bark of Zizyphus nummularia (Rhamnaceae) is traditionally used as an anti-inflammatory agent. The current study aimed to explore the anti-inflammatory activity (in vivo) of a crude ethanolic extract (EE) and the pure identified octadecahydro-picene-2,3,14,15-tetranone (IC) in the root bark of Z. nummularia. IC was further subjected to suitable in vitro and in silico studies to find out the mechanistic pharmacology.MethodsEE (100 and 200 mg/kg, p.o.) and (IC) (400 and 600 μg/kg, p.o.) were subjected to in vivo anti-inflammatory assays to evaluate the anti-inflammatory activity and predict the probable mechanism(s) of action. Suitable acute (carrageenan-induced paw edema, arachidonic acid-induced ear edema, xylene-induced ear edema) and chronic (cotton pellet granuloma) models were employed to investigate in vivo the anti-inflammatory activity. Based on in vivo observation, IC was further subjected to in vitro assays to estimate the inhibition of nitric oxide (NO), prostaglandin-E2 (PGE-2) and tumor necrosis factor-α (TNF-α) production in PBS stimulated RAW 264.7 cells. Based on the observation of in vitro studies, finally, ADME prediction and molecular docking studies of IC were performed for better understanding of interaction of IC with TNF-α.ResultsOral administration of EE (100 and 200 mg/kg) exhibited significant inhibition of carrageenan (p < 0.05) and arachidonic acid (p < 0.05) induced oedema, and the reduced the granuloma tissue formation (p < 0.05) in experimental mice. IC (400 and 600 μg/kg, p.o.) exhibited significant (p < 0.01) inhibition of carrageenan, xylene and arachidonic acid-induced edema, and reduced the granuloma tissue formation. In in vitro assays, IC caused a concentration-dependent inhibition of LPS stimulated NO (up to ~ 67.4 % at 50 μM) and TNF-α (~84.5 % at 50 μM) production. However, the PGE-2 inhibition did not follow dose dependent pattern. Based on in vitro observations, the molecular docking has been performed on the basis of interaction with TNF-α. In in silico studies, it was observed that IC showed hydrogen bonding with GLN 47 amino acid residue of TNF-α protein.ConclusionsIC possibly produces anti-inflammatory activity through inhibition of TNF-α and NO production.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0942-7) contains supplementary material, which is available to authorized users.
“…8 ). The similar types of molecular docking were reported earlier to understand the probable interactions between TNF-α protein and IC [ 39 , 40 ]. Fig.…”
BackgroundThe root bark of Zizyphus nummularia (Rhamnaceae) is traditionally used as an anti-inflammatory agent. The current study aimed to explore the anti-inflammatory activity (in vivo) of a crude ethanolic extract (EE) and the pure identified octadecahydro-picene-2,3,14,15-tetranone (IC) in the root bark of Z. nummularia. IC was further subjected to suitable in vitro and in silico studies to find out the mechanistic pharmacology.MethodsEE (100 and 200 mg/kg, p.o.) and (IC) (400 and 600 μg/kg, p.o.) were subjected to in vivo anti-inflammatory assays to evaluate the anti-inflammatory activity and predict the probable mechanism(s) of action. Suitable acute (carrageenan-induced paw edema, arachidonic acid-induced ear edema, xylene-induced ear edema) and chronic (cotton pellet granuloma) models were employed to investigate in vivo the anti-inflammatory activity. Based on in vivo observation, IC was further subjected to in vitro assays to estimate the inhibition of nitric oxide (NO), prostaglandin-E2 (PGE-2) and tumor necrosis factor-α (TNF-α) production in PBS stimulated RAW 264.7 cells. Based on the observation of in vitro studies, finally, ADME prediction and molecular docking studies of IC were performed for better understanding of interaction of IC with TNF-α.ResultsOral administration of EE (100 and 200 mg/kg) exhibited significant inhibition of carrageenan (p < 0.05) and arachidonic acid (p < 0.05) induced oedema, and the reduced the granuloma tissue formation (p < 0.05) in experimental mice. IC (400 and 600 μg/kg, p.o.) exhibited significant (p < 0.01) inhibition of carrageenan, xylene and arachidonic acid-induced edema, and reduced the granuloma tissue formation. In in vitro assays, IC caused a concentration-dependent inhibition of LPS stimulated NO (up to ~ 67.4 % at 50 μM) and TNF-α (~84.5 % at 50 μM) production. However, the PGE-2 inhibition did not follow dose dependent pattern. Based on in vitro observations, the molecular docking has been performed on the basis of interaction with TNF-α. In in silico studies, it was observed that IC showed hydrogen bonding with GLN 47 amino acid residue of TNF-α protein.ConclusionsIC possibly produces anti-inflammatory activity through inhibition of TNF-α and NO production.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0942-7) contains supplementary material, which is available to authorized users.
“…The first step of the synthesis involves the subsequent acylation of 2-aminothiophenol using chloroacetyl chloride in chloroform to form 2Hbenzo[b] [1,4]thiazin-3(4H)-one [1]. Compound 1 was treated with propargyl bromide in the presence of base in acetone to afford compound 2 in good yield [36]. The oxidation of sulfur in compound 2 with 3-chlorobenzoperoxoic acid (m-CPBA) in dichloromethane at room temperature afforded compound 3 in good yield [37].…”
A series of novel 2H-benzo[b][1,4]thiazin-3(4H)-one derived from 1,4-disubstituted 1,2,3-triazole derivatives (4a-j and 5a-j) were synthesized using Cu(I) catalyzed azide alkyne cyclization (CuAAC) reaction of the compounds 2 and 3 with various aromatic azides. The examination of in vitro anticancer activity revealed that the compounds 4d and 5d were found to possess a broad spectrum of anticancer activity against three cell lines MCF-7, HeLa and IMR-32 with IC50 values ranging from 26.28 ± 1.5 to 32.06 ± 0.3 M mL-1, respectively. The remaining compounds have shown good to moderate activity against the tested cell lines.
“…A similar effect was observed with indomethacin (1840 pg/ml) and BOA treatment on the TNF-α level. TNF-α inhibitory effect of certain BOA derivatives was compared using indomethacin as a positive control [28]. Hence, we believe that it is important to determine its acute oral safety.…”
Section: Arumugam and Thiruganasambanthammentioning
Objective: Acanthus ilicifolius Linn. (Acanthaceae) is a medicinal mangrove plant used in the treatment of inflammation. Previous phytochemical studies have identified 2-benzoxazolinone (BOA) from the leaves of A. ilicifolius. In the present study, we attempted to standardize the supercritical CO2 leaf extract of A. ilicifolius (SCFE-AI) for BOA content and investigate the tumor necrosis factor-α (TNF-α) inhibitory effect of SCFE-AI and BOA on the lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. The acute oral toxicity of SCFE-AI and BOA was also established.Methods: SCFE-AI was standardized for BOA content using high-performance thin-layer chromatography (HPTLC) method. The cytotoxicity of SCFE-AI and BOA was evaluated using MTS colorimetric method. The in vitro anti-inflammatory effect of SCFE-AI and BOA on TNF-α production in LPS-activated RAW 264.7 cells was quantified using ELISA method. Acute oral toxicity studies were performed following the Organization for Economic Co-operation and Development test guideline No. 423.Results: The amount of BOA was found 0.8% w/w of SCFE-AI. The RAW 264.7 cell viability was unaffected by SCFE-AI and BOA treatments within a concentration range <1000 mg/ml after 24 h incubation. SCFE-AI decreased the production of TNF-α in a dose-dependent manner compared to BOA. The LD50 value for SCFE-AI was found to be >2000 mg/kg and ranges from 300 to 2000 mg/kg with BOA.Conclusion: The HPTLC chromatogram could serve as an analytical tool for authentication and quantification of BOA content. The anti-inflammatory mechanism of A. ilicifolius might be through the inhibition of TNF-α production.
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