screening of polyphenols targeting the RhoA protein as a potential liver cancer treatment.

Rukhsana Tabassum, Erum Dilshad
Author Information
  1. Rukhsana Tabassum: Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology (CUST), Islamabad, Pakistan.
  2. Erum Dilshad: Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology (CUST), Islamabad, Pakistan.

Abstract

Objective: Because aberrant Rho GTPase signaling has been associated with multiple cancers, it was investigated as a potential target for liver cancer treatment drugs. The important medicinal plant , found in the Karakoram Mountains, is believed to contain polyphenols that inhibit RhoA protein, thus potentially eliciting effects against liver cancer.
Methods: Polyphenols were identified in the methanolic extract of with HPLC, then screened for their anticancer potential against the RhoA protein through molecular docking and molecular dynamic simulations. The RMSD and RMSF values for each selected compound were determined, and ADMET characteristics were analyzed.
Results: The polyphenols gallic acid, salicylic acid, caffeic acid, kaempferol, rutin, quercetin, coumarin, ferulic acid, sinapic acid, HB acid, vanillic acid, and chlorogenic acid were found in the methanolic extract of . On the basis of Lipinski's rule of five, the Vina score, and the cavity size, we chose five ligands with favorable features for further research. Caffeic acid was the most promising compound, on the basis of favorable ADMET qualities, and the best docking score and MD simulation results.
Conclusion: Caffeic acid remained intact and bound the protein structure throughout the simulation run, thus demonstrating a robust interaction between the protein and ligand, and indicating a possible inhibitory effect. Therefore, this compound might have the greatest ability to inhibit the RhoA protein. Further research is required to examine caffeic acid as a potential medication option for future drug development.

Keywords

References

  1. Acta Pharmacol Sin. 2020 Jan;41(1):138-144 [PMID: 31263275]
  2. Curr Protoc Pharmacol. 2010 Jun;Chapter 9:Unit 9.12 [PMID: 22294375]
  3. PLoS One. 2021 Jul 14;16(7):e0254035 [PMID: 34260631]
  4. J Hepatol. 2015 Jun;62(6):1412-9 [PMID: 25623823]
  5. Curr Protoc. 2021 Aug;1(8):e217 [PMID: 34370395]
  6. Am J Cancer Res. 2020 Mar 01;10(3):884-896 [PMID: 32266097]
  7. Sci Rep. 2022 Mar 1;12(1):3395 [PMID: 35233058]
  8. Molecules. 2023 Apr 20;28(8): [PMID: 37110817]
  9. Annu Rev Nutr. 2018 Aug 21;38:17-39 [PMID: 29801420]
  10. J Cheminform. 2021 Jun 9;13(1):43 [PMID: 34108002]
  11. Molecules. 2023 Nov 22;28(23): [PMID: 38067448]
  12. Cancer Treat Rev. 2012 Feb;38(1):76-87 [PMID: 21481535]
  13. Molecules. 2022 Nov 28;27(23): [PMID: 36500403]
  14. Int J Mol Sci. 2019 Sep 04;20(18): [PMID: 31487867]
  15. Drug Dev Ind Pharm. 2024 Sep 10;:1-10 [PMID: 39226126]
  16. RSC Adv. 2022 Apr 27;12(20):12913-12931 [PMID: 35496328]
  17. Sci Transl Med. 2014 Mar 5;6(226):226ra32 [PMID: 24598590]
  18. Int J Oncol. 2020 Jul;57(1):249-263 [PMID: 32319605]
  19. Cancer Epidemiol Biomarkers Prev. 2011 Nov;20(11):2362-8 [PMID: 21921256]
  20. Cancer Manag Res. 2020 Sep 28;12:8599-8611 [PMID: 33061565]
  21. Molecules. 2023 Sep 16;28(18): [PMID: 37764441]
  22. Int J Mol Sci. 2017 Feb 21;18(2): [PMID: 28230778]
  23. Pharmacol Ther. 2018 Mar;183:1-21 [PMID: 28911825]
  24. Biomed Pharmacother. 2024 Jun;175:116638 [PMID: 38688169]
  25. Front Oncol. 2019 Jun 21;9:541 [PMID: 31293975]
  26. BMC Pharmacol Toxicol. 2021 Nov 2;22(1):68 [PMID: 34727985]
  27. Mini Rev Med Chem. 2023;23(3):246-264 [PMID: 35549880]
  28. Oncotarget. 2016 Dec 6;7(49):81435-81451 [PMID: 27806312]
  29. J Lab Clin Med. 2005 Jun;145(6):316-22 [PMID: 15976760]
  30. J Intercult Ethnopharmacol. 2017 Jul 12;6(3):296-310 [PMID: 28894629]
  31. J Pharm Biomed Anal. 2008 May 12;47(1):31-8 [PMID: 18194847]
  32. Dose Response. 2023 Jul 5;21(3):15593258231187357 [PMID: 37435595]
  33. Aging (Albany NY). 2019 Jul 22;11(14):5158-5172 [PMID: 31339860]
  34. Molecules. 2023 Feb 13;28(4): [PMID: 36838758]
  35. Molecules. 2020 Mar 05;25(5): [PMID: 32150954]
  36. Small GTPases. 2014;5:e29019 [PMID: 25036871]
  37. Front Cell Dev Biol. 2020 Apr 03;8:222 [PMID: 32309283]
  38. Cell. 2000 Jan 7;100(1):57-70 [PMID: 10647931]
  39. Sci Rep. 2024 Apr 2;14(1):7749 [PMID: 38565703]
  40. Exp Hematol Oncol. 2022 Nov 8;11(1):91 [PMID: 36348464]
  41. Biochim Biophys Acta Rev Cancer. 2020 Jan;1873(1):188314 [PMID: 31682895]
  42. Nucleic Acids Res. 2022 Jul 5;50(W1):W159-W164 [PMID: 35609983]
  43. Nat Prod Res. 2024 Jul 1;:1-9 [PMID: 38949792]
  44. BioTechnologia (Pozn). 2023 Jun 26;104(2):183-198 [PMID: 37427027]

Word Cloud

Created with Highcharts 10.0.0acidproteinRhoApotentialcancerliverpolyphenolscompoundtreatmentfoundinhibitthusPolyphenolsmethanolicextractmoleculardockingADMETcaffeicbasisfivescorefavorableresearchCaffeicsimulationscreeningObjective:aberrantRhoGTPasesignalingassociatedmultiplecancersinvestigatedtargetdrugsimportantmedicinalplantKarakoramMountainsbelievedcontainpotentiallyelicitingeffectsMethods:identifiedHPLCscreenedanticancerdynamicsimulationsRMSDRMSFvaluesselecteddeterminedcharacteristicsanalyzedResults:gallicsalicylickaempferolrutinquercetincoumarinferulicsinapicHBvanillicchlorogenicLipinski'sruleVinacavitysizechoseligandsfeaturespromisingqualitiesbestMDresultsConclusion:remainedintactboundstructurethroughoutrundemonstratingrobustinteractionligandindicatingpossibleinhibitoryeffectThereforemightgreatestabilityrequiredexaminemedicationoptionfuturedrugdevelopmenttargetingDrugdiscoveryHrhamnoidesLiverPhytochemical

Similar Articles

Cited By