Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular Docking of Novel Furan-based Derivatives as Potential TNF-α Production Inhibitors

Satish Bhoge; Prabal Pratap Singh; Deepak Das; Yakub Ali; Abhijeet Dhulap

doi:10.2174/1570180820666230828151523

ISSN: 1570-1808
E-ISSN: 1875-628X

Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular Docking of Novel Furan-based Derivatives as Potential TNF-α Production Inhibitors
Authors: Satish Bhoge¹, Prabal Pratap Singh¹, Deepak Das¹, Yakub Ali² and Abhijeet Dhulap³
View Affiliations Hide Affiliations

Affiliations: ¹ Department of Chemistry, GLA University, Mathura, India ; ² Department of Chemistry, Jamia Hamdard University, Delhi, India ; ³ Department of R&D, National Chemical Laboratory, Pune, India
Source: Letters in Drug Design & Discovery, Volume 21, Issue 14, Nov 2024, p. 2916 - 2925
DOI: https://doi.org/10.2174/1570180820666230828151523
- Received: 16 Feb 2023
- Accepted: 24 Jul 2023
- Available online: 01 Nov 2024

Abstract

Introduction

Inflammation is the first response and an alarming signal for the onset of chronic disease. Most of the anti-inflammatory drugs available in the market are reported to have undesirable gastrointestinal toxicities. Therefore, it is of urgent significance to develop anti-inflammatory drugs with low toxicity and good efficacy.

Methods

We created a targeted scaffold based on a literature review by combining the different structural characteristics of furan and benzyl amides into a single pharmacophore. A series of eighteen furan-based derivatives (1-18) were designed, synthesized for in vitro and in vivo anti-inflammatory activity. The characterization of synthesized compounds was elucidated by techniques like ¹H-NMR, ¹³C-NMR, FT-IR and MS.

Results

The synthetic compounds were examined through molecular docking studies on TNF-α for probable binding mode and interactions with hydrophilic and hydrophobic pocket of TNF-α in comparison to standard drug (Indomethacin).

Conclusion

When compared to the standard treatment, compounds 18, 15 and 9 displayed a remarkable inhibitory effect on the production of TNF-α and in vivo inflammatory activity with no damage to stomach and reduction of LPO. The compounds 18, 15 and 9 might be a good consideration for potential anti-inflammatory agents.

Article metrics loading...

/content/journals/lddd/10.2174/1570180820666230828151523

2024-11-01

2024-11-19

From This Site

/content/journals/lddd/10.2174/1570180820666230828151523

dcterms_title,dcterms_subject,pub_keyword

-contentType:Contributor -contentType:Concept -contentType:Institution

10

5

Full text loading...

References

ChyanY.J. ChuangL.M. Dipeptidyl peptidase-IV inhibitors: An evolving treatment for type 2 diabetes from the incretin concept.Recent Pat. Endocr. Metab. Immune Drug Discov.200711152410.2174/187221407779814570
[Google Scholar]
NathanC. DingA. Nonresolving inflammation.Cell2010140687188210.1016/j.cell.2010.02.029 20303877
[Google Scholar]
FardM.T. ArulselvanP. KarthivashanG. AdamS.K. FakuraziS. Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages.Pharmacogn. Mag.2015114S556S563 27013794
[Google Scholar]
GanL. ZhengY. DengL. SunP. YeJ. WeiX. LiuF. YuL. YeW. FanC. LiuJ. ZhangW. Diterpenoid lactones with anti-inflammatory effects from the aerial parts of Andrographis paniculata.Molecules20192415272610.3390/molecules24152726 31357563
[Google Scholar]
ZelováH. HošekJ. TNF-α signalling and inflammation: Interactions between old acquaintances.Inflamm. Res.201362764165110.1007/s00011‑013‑0633‑0 23685857
[Google Scholar]
GraningerW. SmolenJ. Treatment of rheumatoid arthritis by TNF-blocking agents.Int. Arch. Allergy Immunol.20021271101410.1159/000048164 11893849
[Google Scholar]
PearceG.J. ChikanzaI.C. Targeting tumour necrosis factor in the treatment of rheumatoid arthritis.BioDrugs200115313914910.2165/00063030‑200115030‑00001 11437680
[Google Scholar]
TsutsumiS. GotohT. TomisatoW. MimaS. HoshinoT. HwangH-J. TakenakaH. TsuchiyaT. MoriM. MizushimaT. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis.Cell Death Differ.20041191009101610.1038/sj.cdd.4401436 15131590
[Google Scholar]
BinduS. MazumderS. BandyopadhyayU. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective.Biochem. Pharmacol.202018011414710.1016/j.bcp.2020.114147 32653589
[Google Scholar]
SharmaS. KumarD. SinghG. MongaV. KumarB. Recent advancements in the development of heterocyclic anti-inflammatory agents.Eur. J. Med. Chem.202020011243810.1016/j.ejmech.2020.112438 32485533
[Google Scholar]
PatelN.R. PatelD.V. Synthesis and biological activities of vicinal diaryl furans.Vicinal. Diaryl. Subst. Heterocy.Elsevier201822124410.1016/B978‑0‑08‑102237‑5.00007‑9
[Google Scholar]
HaiderS. AlamM.S. HamidM. UmarS. KumarD. NazreenS. Synthesis of novel amide containing Schiff’s bases of 5-(4-chloro-phenyl)-furan-2-carboxaldehyde: Their in vivo anti-inflammatory, antioxidant and antinociceptive activities with ulcerogenic risk evaluation.J. Rep. Pharma. Sci.2018714463
[Google Scholar]
PomelV. KlicicJ. CoviniD. ChurchD.D. ShawJ.P. RoulinK. Burgat-CharvillonF. ValognesD. CampsM. ChabertC. GillieronC. FrançonB. PerrinD. LeroyD. GretenerD. NicholsA. VitteP.A. CarboniS. RommelC. SchwarzM.K. RückleT. Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma.J. Med. Chem.200649133857387110.1021/jm0601598 16789742
[Google Scholar]
LinZ. LiH. LuoH. ZhangY. LuoW. Benzylamine and methylamine, substrates of semicarbazide-sensitive amine oxidase, attenuate inflammatory response induced by lipopolysaccharide.Int. Immunopharmacol.20111181079108910.1016/j.intimp.2011.03.002 21414430
[Google Scholar]
AliY. AlamM.S. HamidH. HusainA. KharbandaC. BanoS. NazreenS. HaiderS. Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation of Aporosa lindleyana Baill bark extract.J. Ethnopharmacol.201415531513152110.1016/j.jep.2014.07.035 25124276
[Google Scholar]
SlyvkaN. SaliyevaL. HolotaS. KhylukD. TkachukV. VovkM. Sulfones of pyridinyloxy-substituted imidazo[2,1-b][1,3]thiazines: Synthesis, anti-inflammatory activity evaluation in vivo and docking studies.Lett. Drug Des. Discov.202320111867187510.2174/1570180819666220812144409
[Google Scholar]
PatelP.K. SahuJ. ChandelS.S. A detailed review on nociceptive models for the screening of analgesic activity in experimental animals.Int J Neurol Phys Ther.2016264450
[Google Scholar]
HamidI. NadeemH. AnsariS.F. KhiljeeS. AbbasiI. BukhariA. ArifM. ImranM. 2-substituted benzoxazoles as potent anti-inflammatory agents: Synthesis, molecular docking and in vivo anti-ulcerogenic studies.Med. Chem.202218779180910.2174/1573406418666211220125344 34931968
[Google Scholar]
BansalA. BaliA. BalainiA. Synthesis and evaluation of substituted aryl thiazoles with antioxidant potential as gastro-sparing anti-inflammatory agents.Lett. Drug Des. Discov.202017121566157810.2174/1570180817999200706005247
[Google Scholar]
HollaB.S. MaliniK.V. SarojiniB.K. PoojaryB. A novel three‐component synthesis of triazinothiazolones.Synth. Commun.200535333334010.1081/SCC‑200048903
[Google Scholar]
HeM. LiY.J. ShaoJ. FuC. LiY.S. CuiZ.N. 2,5-Disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety as potent α-glucosidase inhibitors.Bioorg. Chem.202313110629810.1016/j.bioorg.2022.106298 36455481
[Google Scholar]
AdelusiT.I. OyedeleA.Q.K. BoyenleI.D. OgunlanaA.T. AdeyemiR.O. UkachiC.D. IdrisM.O. OlaobaO.T. AdedotunI.O. KolawoleO.E. XiaoxingY. Abdul-HammedM. Molecular modeling in drug discovery.Inform. Med. Unlocked20222910088010.1016/j.imu.2022.100880
[Google Scholar]

/content/journals/lddd/10.2174/1570180820666230828151523

Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular Docking of Novel Furan-based Derivatives as Potential TNF-α Production Inhibitors

Letters in Drug Design & Discovery 21, 2916 (2024); https://doi.org/10.2174/1570180820666230828151523

/content/journals/lddd/10.2174/1570180820666230828151523

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

Article Type: Research Article

Keyword(s): analgesic; anti-inflammatory; Furan-based derivatives; lipid peroxidation; TNF-α; ulcerogenic

Design, Synthesis, Anti-inflammatory Evaluation and In silico Molecular Docking of Novel Furan-based Derivatives as Potential TNF-α Production Inhibitors

Abstract

From This Site

Supplementary material is available on the publisher's website along with the published article.

Most Read This Month

Most Cited Most Cited RSS feed

Discovery, Structural Determination and Anticancer Activities of Lactucinlike Guaianolides

Thermodynamic Aspects of Cancer: Possible Role of Negative Entropy in Tumor Growth, its Relation to Kinetic and Genetic Resistance

Immunomodulatory Properties of Synthetic Imidazolone Derivatives

Design and Prediction of ADME/Tox Properties of Novel Magnolol Derivatives as Anticancer Agents for NSCLC Using 3D-QSAR, Molecular Docking, MOLCAD and MM-GBSA Studies

Redox Active Iron at the Center of Oxidative Stress in Alzheimer Disease

Identifying Protein Binding Sites and Optimal Ligands

Phenyldihydroxypyrimidines as HCV NS5B RNA Dependent RNA Polymerase Inhibitors. Part I: Amides and Ureas

Anti-cancer Potential of Pleurotus Mushroom: Detailed Insight on the Potential Bioactive Molecules, In vitro-In vivo Studies, and Formulation

Phenyldihydroxypyrimidines as HCV NS5B RNA Dependent RNA Polymerase Inhibitors. Part II: Sulfonamides

Selection of a Catalytically Active Enzyme In Vivo Via Phage Display of its Product