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2000
Volume 23, Issue 3
  • ISSN: 1871-5230
  • E-ISSN: 1875-614X

Abstract

Background

Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cascade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflammatory activity dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism.

Methods

RAW 264.7 macrophages were collected from NCC, Pune, for experiments. The IC values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macrophages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney.

Results

The present study described the and biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC values 0.092 and 0.136 µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selectivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% compared with standard 40.13% granuloma inhibition.

Conclusion

The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

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2025-09-09

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References

  1. HariharanR. OdjidjaE.N. ScottD. ShivappaN. HébertJ.R. HodgeA. de CourtenB. The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases.Obes. Rev.2022231e1334910.1111/obr.1334934708499
     [Google Scholar]
  2. RothG. Global Burden of Disease Collaborative Network Global burden of disease study 2017 (GBD 2017) results. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2018.Lancet20183921736178810.1016/S0140‑6736(18)32203‑7
     [Google Scholar]
  3. PhillipsC.M. ChenL.W. HeudeB. BernardJ.Y. HarveyN.C. DuijtsL. Mensink-BoutS.M. PolanskaK. MancanoG. SudermanM. ShivappaN. HébertJ.R. Dietary inflammatory index and non-communicable disease risk: A narrative review.Nutrients2019118187310.3390/nu1108187331408965
     [Google Scholar]
  4. HariziH. CorcuffJ.B. GualdeN. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology.Trends Mol. Med.2008141046146910.1016/j.molmed.2008.08.00518774339
     [Google Scholar]
  5. de GaetanoG. DonatiM.B. CerlettiC. Prevention of thrombosis and vascular inflammation: Benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors.Trends Pharmacol. Sci.200324524525210.1016/S0165‑6147(03)00077‑412767724
     [Google Scholar]
  6. HawkeyC.J. COX-2 inhibitors.Lancet1999353914930731410.1016/S0140‑6736(98)12154‑29929039
     [Google Scholar]
  7. FiorucciS. MeliR. BucciM. CirinoG. Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy? 1 1Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; COX, cyclooxygenase; LT, leukotriene; 5-LOX, 5-lipoxygenase; PG, prostaglandin; DFU, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsuphonyl)-phenyl-2(5H)-furanone; and DFP, diisopropyl fluorophosphate.Biochem. Pharmacol.200162111433143810.1016/S0006‑2952(01)00747‑X11728379
     [Google Scholar]
  8. CharlierC. MichauxC. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs.Eur. J. Med. Chem.2003387-864565910.1016/S0223‑5234(03)00115‑612932896
     [Google Scholar]
  9. JulémontF. DognéJ.M. PirotteB. LevalX. Recent development in the field of dual COX / 5-LOX inhibitors.Mini Rev. Med. Chem.20044663363810.2174/138955704340374715279597
     [Google Scholar]
  10. ZhangJ.M. AnJ. Cytokines, inflammation, and pain.Int. Anesthesiol. Clin.2007452273710.1097/AIA.0b013e318034194e17426506
     [Google Scholar]
  11. ZhuangC. ZhangW. ShengC. ZhangW. XingC. MiaoZ. Chalcone: A privileged structure in medicinal chemistry.Chem. Rev.2017117127762781010.1021/acs.chemrev.7b0002028488435
     [Google Scholar]
  12. RozmerZ. PerjésiP. Naturally occurring chalcones and their biological activities.Phytochem. Rev.20161518712010.1007/s11101‑014‑9387‑8
     [Google Scholar]
  13. KostaneckiV.S. TamborJ. About the six isomeric monooxybenzalacetophenones (monooxychalcones).Ber. Dtsch. Chem. Ges.18993221921192610.1002/cber.18990320293
     [Google Scholar]
  14. SinghalM. PaulA. SinghH. Synthesis and characterization of some novel chalcone derivatives: An intermediate for various heterocyclic compounds.Int. J. Pharm. Investig.2011111723071911
     [Google Scholar]
  15. Díaz-TielasC. GrañaE. ReigosaM.J. Sánchez-MoreirasA.M. Biological activities and novel applications of chalcones.Planta Daninha201634360761610.1590/s0100‑83582016340300022
     [Google Scholar]
  16. PrasharH. ChawlaA. SharmaA.K. KharbR. Chalcone as a versatile moiety for diverse pharmacological activities.Int. J. Pharm. Sci. Res.2012371913
     [Google Scholar]
  17. AwaadA.S. El-MeligyR.M. SolimanG.A. Natural products in treatment of ulcerative colitis and peptic ulcer.J. Saudi Chem. Soc.201317110112410.1016/j.jscs.2012.03.002
     [Google Scholar]
  18. ur RashidH. XuY. AhmadN. MuhammadY. WangL. Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κb activities.Bioorg. Chem.20198733536510.1016/j.bioorg.2019.03.03330921740
     [Google Scholar]
  19. MittalR. SharmaS. MittalA. KumarS. KushwahA.S. Virtual screening, molecular docking, and physiochemical analysis of novel 1,3-diphenyl-2-propene-1-one as dual COX-2/5-LOX inhibitors.Lett. Drug Des. Discov.202421227028810.2174/1570180819666220523093435
     [Google Scholar]
  20. KangS.R. HanD.Y. ParkK.I. ParkH.S. Suppressive effect on lipopolysaccharide-induced proinflammatory mediators by citrus aurantium L. in macrophage RAW 264.7 cells via NF-B signal pathway.Evid. Based Complement. Alternat. Med.201124859210.1155/2011/248592
     [Google Scholar]
  21. YoonS.B. LeeY.J. ParkS.K. KimH.C. BaeH. KimH.M. KoS.G. ChoiH.Y. OhM.S. ParkW. Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages.J. Ethnopharmacol.2009125228629010.1016/j.jep.2009.06.02719577625
     [Google Scholar]
  22. KarkiR. ParkC.H. KimD.W. Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7).J. Integr. Med.201311424625210.3736/jintegrmed201303623867243
     [Google Scholar]
  23. LeeM.Y. ParkB.Y. KwonO.K. YukJ.E. OhS.R. KimH.S. LeeH.K. AhnK.S. Anti-inflammatory activity of (−)-aptosimon isolated from Daphne genkwa in RAW264.7 cells.Int. Immunopharmacol.200997-887888510.1016/j.intimp.2009.03.01219328870
     [Google Scholar]
  24. WuL. FanN. LinM. ChuI. HuangS. HuC.Y. HanS. Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators.J. Agric. Food Chem.20085672341234910.1021/jf073057e18321049
     [Google Scholar]
  25. WinterC.A. RisleyE.A. NussG.W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs.Exp. Biol. Med.1962111354454710.3181/00379727‑111‑2784914001233
     [Google Scholar]
  26. AbdelrahmanM.H. YoussifB.G.M. abdelgawadM.A. AbdelazeemA.H. IbrahimH.M. MoustafaA.E.G.A. TreambluL. BukhariS.N.A. Synthesis, biological evaluation, docking study and ulcerogenicity profiling of some novel quinoline-2-carboxamides as dual COXs/LOX inhibitors endowed with anti-inflammatory activity.Eur. J. Med. Chem.201712797298510.1016/j.ejmech.2016.11.00627837994
     [Google Scholar]
  27. GeorgeL. RamasamyT. ManickamV. IyerS.K. RadhakrishnanV. Novel phenanthridine (PHE-4i) derivative inhibits carrageenan-induced rat hind paw oedema through suppression of hydrogen sulfide.Inflammopharmacology201624417318010.1007/s10787‑016‑0273‑427380491
     [Google Scholar]
  28. XuG.L. LiuF. AoG.Z. HeS.Y. JuM. ZhaoY. XueT. Anti-inflammatory effects and gastrointestinal safety of NNU-hdpa, a novel dual COX/5-LOX inhibitor.Eur. J. Pharmacol.20096111-310010610.1016/j.ejphar.2009.03.06219345206
     [Google Scholar]
  29. SabiuS. GarubaT. SunmonuT. AjaniE. SulymanA. NurainI. BalogunA. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin a nd Ficus exasperata. Toxicol. Rep.2015226126710.1016/j.toxrep.2015.01.00228962358
     [Google Scholar]
  30. LeeE.S. ParkB.C. PaekS.H. LeeY.S. BasnetA. JinD.Q. ChoiH.G. YongC.S. KimJ.A. Potent analgesic and anti-inflammatory activities of 1-furan-2-yl-3-pyridin-2-yl-propenone with gastric ulcer sparing effect.Biol. Pharm. Bull.200629236136410.1248/bpb.29.36116462046
     [Google Scholar]
  31. ZhaoJ. MaitituersunA. LiC. LiQ. XuF. LiuT. Evaluation on analgesic and anti-inflammatory activities of total flavonoids from Juniperus sabina.Evid. Based Complement. Alternat. Med.201820181910.1155/2018/796530630069226
     [Google Scholar]
  32. ChenS. MukoyamaT. SatoN. YamagataS.I. AraiY. SatohN. UedaS. Induction of nephrotoxic serum nephritis in inbred mice and suppressive effect of colchicine on the development of this nephritis.Pharmacol. Res.200245431932410.1006/phrs.2002.094812030796
     [Google Scholar]
  33. NazM. RehmanN. Nazam AnsariM. KamalM. GanaieM.A. AwaadA.S. AlqasoumiS.I. Comparative study of subchronic toxicities of mosquito repellents (coils, mats and liquids) on vital organs in Swiss albino mice.Saudi Pharm. J.201927334835310.1016/j.jsps.2018.12.00230976177
     [Google Scholar]
  34. ShrivastavaS.K. SrivastavaP. BandreshR. TripathiP.N. TripathiA. Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase inhibitor for anti-inflammatory activity.Bioorg. Med. Chem.201725164424443210.1016/j.bmc.2017.06.02728669741
     [Google Scholar]
  35. GangulyA.K. A method for quantitative assessment of experimentally produced ulcers in the stomach of albino rats.Experientia196925111224122410.1007/BF019002905357845
     [Google Scholar]
  36. KamilM. FatimaA. UllahS. AliG. KhanR. IsmailN. QayumM. IrimieM. DinuC.G. AhmedahH.T. CocuzM.E. Toxicological evaluation of novel cyclohexenone derivative in an animal model through histopathological and biochemical techniques.Toxics20219611910.3390/toxics906011934070633
     [Google Scholar]
  37. TasneemS. LiuB. LiB. ChoudharyM.I. WangW. Molecular pharmacology of inflammation: Medicinal plants as anti-inflammatory agents.Pharmacol. Res.201913912614010.1016/j.phrs.2018.11.00130395947
     [Google Scholar]
  38. OngC.K.S. LirkP. TanC.H. SeymourR.A. An evidence-based update on nonsteroidal anti-inflammatory drugs.Clin. Med. Res.200751193410.3121/cmr.2007.69817456832
     [Google Scholar]
  39. SostresC. GargalloC.J. ArroyoM.T. LanasA. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract.Best Pract. Res. Clin. Gastroenterol.201024212113210.1016/j.bpg.2009.11.00520227026
     [Google Scholar]
  40. XuG.L. LiuF. ZhaoY. AoG.Z. XiL. JuM. XueT. Biological evaluation of 2-(4-amino-phenyl)-3-(3,5-dihydroxylphenyl) propenoic acid.Basic Clin. Pharmacol. Toxicol.2009105535035610.1111/j.1742‑7843.2009.00463.x19744157
     [Google Scholar]
  41. YangJ. LiS. XieC. YeH. TangH. ChenL. PengA. Anti-inflammatory activity of ethyl acetate fraction of the seeds of Brucea Javanica.J. Ethnopharmacol.2013147244244610.1016/j.jep.2013.03.03423538165
     [Google Scholar]
  42. KarimN. KhanI. KhanW. KhanI. KhanA. HalimS.A. KhanH. HussainJ. Al-HarrasiA. Anti-nociceptive and anti-inflammatory activities of asparacosin a involve selective cyclooxygenase 2 and inflammatory cytokines inhibition: An in-vitro, in-vivo, and in-silico approach.Front. Immunol.20191058110.3389/fimmu.2019.0058130972073
     [Google Scholar]
  43. NegiP. AgarwalS. GargP. AliA. KulshresthaS. In vivo models of understanding inflammation (in vivo methods for inflammation)Recent Developments in Anti-Inflammatory Therapy202331533010.1016/B978‑0‑323‑99988‑5.00017‑6
     [Google Scholar]
  44. SengarN. JoshiA. PrasadS.K. HemalathaS. Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac.J. Ethnopharmacol.201516014014810.1016/j.jep.2014.11.03925479154
     [Google Scholar]
  45. SolankiH.K. ShahD.A. MaheriyaP.M. PatelC.A. Evaluation of anti-inflammatory activity of probiotic on carrageenan-induced paw edema in Wistar rats.Int. J. Biol. Macromol.2015721277128210.1016/j.ijbiomac.2014.09.05925316426
     [Google Scholar]
  46. CongH.H. KhaziakhmetovaV.N. ZigashinaL.E. Rat paw oedema modeling and NSAIDs: Timing of effects.Int. J. Risk Saf. Med.201527s1Suppl. 1S76S7710.3233/JRS‑15069726639722
     [Google Scholar]
  47. SpectorW.G. The granulomatous inflammatory exudate.Int. Rev. Exp. Pathol.196981554904706
     [Google Scholar]
  48. SwingleK.F. ShidemanF.E. Phases of the inflammatory response to subcutaneous implantation of a cotton pellet and their modification by certain anti-inflammatory agents.J. Pharmacol. Exp. Ther.197218312262344562620
     [Google Scholar]
  49. LiW. HuangH. ZhangY. FanT. LiuX. XingW. NiuX. Anti-inflammatory effect of tetrahydrocoptisine from Corydalis impatiens is a function of possible inhibition of TNF-α, IL-6 and NO production in lipopolysaccharide-stimulated peritoneal macrophages through inhibiting NF-κB activation and MAPK pathway.Eur. J. Pharmacol.20137151-3627110.1016/j.ejphar.2013.06.01723810685
     [Google Scholar]
  50. LiaoJ.C. TsaiJ.C. PengW.H. ChiuY.J. SungP.J. TsuzokiM. KuoY.H. Anti-inflammatory activity of N-(3-florophenyl)ethylcaffeamide in mice.Int. J. Mol. Sci.2013148151991521110.3390/ijms14081519923887648
     [Google Scholar]
  51. VysakhA. JayeshK. HelenL.R. JyothisM. LathaM.S. Acute oral toxicity and anti-inflammatory evaluation of methanolic extract of Rotula aquatica roots in Wistar rats.J. Ayurveda Integr. Med.2020111455210.1016/j.jaim.2017.09.00730120055
     [Google Scholar]
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Novel Dual COX-2/5-LOX Inhibitory Activity by Chalcone Derivatives: A Safe and Efficacious Anti-inflammatory Agent
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 23, 174 (2024); https://doi.org/10.2174/0118715230301176240605072113
/content/journals/aiaamc/10.2174/0118715230301176240605072113
/content/journals/aiaamc/10.2174/0118715230301176240605072113
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  • Article Type:     Research Article
Keyword(s): anti-inflammatory models; chalcone; DualCOX-2/5-LOX inhibition; gastric safety; indomethacin; inflammation; RAW 264.7 cell lines

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