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Computational approaches to discover a Kaempferol derivative extracted from Senna alexandrina as Escherichia coli enzyme (MurF) inhibitor by molecular docking, molecular dynamics simulation, and ADME-Tox

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Abstract

Escherichia coli is presented in the human intestines as a harmless bacterium, but if it exceeds the normal threshold, it will be pathogenic bacteria causing other pathogens to grow faster; there are also subspecies, each of which causes a different disease, such as intestinal or urinary infections, which can be severe. A theoretical study on the Kaempferol derivative compounds, which belongs to the flavonoids extracted from Senna Alexandrina plant as part of medicinal plant-based drugs and five other derivatives (collected according to literature) against Escherichia coli UDPMurNAc-tripeptide d-alanyl-d-alanine-adding enzyme (MurF) as a therapeutic target. The antibacterial effect of Senna alexandrina was studied using computational molecular docking to investigate the interaction type between Kaempferol derivatives and MurF. In addition, molecular dynamics simulation for M1-Kaempferol derivative and MurF complex show high stability over time (0–100 ns). The toxicity of Kaempferol derivative as a potential drug was determined by ADME-Tox profile for M1-Kaempferol derivative to show their ability to intervene in an antibacterial drug.

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References

  1. Shazia S, Mushtaq A, Muhammad Z, Mir Ajab K, Muhammad A (2012) Authentication of herbal drug Senna (Cassia angustifolia Vahl.): a village pharmacy for Indo-Pak Subcontinent. African J Pharm Pharmacol 6:2299–2308. https://doi.org/10.5897/AJPP12.446

    Article  Google Scholar 

  2. Wang X, Wang T, Pan T et al (2020) Senna alexandrina extract supplementation reverses hepatic oxidative, inflammatory, and apoptotic effects of cadmium chloride administration in rats. Environ Sci Pollut Res 27:5981–5992. https://doi.org/10.1007/s11356-019-07117-3

    Article  CAS  Google Scholar 

  3. Alonso J (2004) Tratado de Fitofármacos y Nutracéuticos, 1st Ed, Editorial Corpus Libros Rosario, Argentina, pp 985–989

  4. Kumar D, Arora S, Verma A (2013) Fatty acid composition and antimicrobial and antioxidant activity of Cassia glauca seed extracts. Int J Phytopharm 4:113–118

    Google Scholar 

  5. Hayashi S, Yoshida A, Tanaka H et al (1980) Analytical studies on the active constituents in crude drugs. IV. Determination of sennosides in Senna and formulations by high-performance liquid chromatography. Chem Pharm Bull 28:406–412. https://doi.org/10.1248/cpb.28.406

    Article  CAS  Google Scholar 

  6. Monkheang P, Sudmoon R, Tanee T, Noikotr K, Bletter N, Chaveerach A (2011) Species diversity, usages, molecular markers and barcode of medicinal Senna species (Fabaceae, Caesalpinioideae) in Thailand. J Med Plant Res 5:6173–6181. https://doi.org/10.5897/JMPR11.1075

    Article  CAS  Google Scholar 

  7. Schulz V, Hänsel R, Tyler VE (2001) Rational phytotherapy: a physician’s guide to herbal medicine, 4th edn. Springer-Verlag, Berlin

    Book  Google Scholar 

  8. Ishibashi F, Tanaka R, Sugihara K et al (2021) Pre-administration of super-low volume polyethylene glycol is as effective as Senna laxative as bowel preparation for colonoscopy: a randomized controlled phase 2 trial. Surg Endosc 36:3141–3151. https://doi.org/10.1007/s00464-021-08617-5

    Article  PubMed  Google Scholar 

  9. Ping QW, Wang ZJ, Tang LY, Fu MH, He Y (2009) A new flavonoid glucoside from Cassia angustifolia. Chin Chem Lett 20:320–321. https://doi.org/10.1016/j.cclet.2008.12.003

    Article  CAS  Google Scholar 

  10. Kaper JB, Nataro JP, Mobley HL (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2:123–140. https://doi.org/10.1038/nrmicro818

    Article  CAS  PubMed  Google Scholar 

  11. Albert MJ, Faruque SM, Faruque AS, Bettelheim KA, Neogi PK, Bhuiyan NA, Kaper JB (1996) Controlled study of cytolethal distending toxin-producing Escherichia coli infections in Bangladeshi children. J Clin Microbiol 34:717–719. https://doi.org/10.1128/jcm.34.3.717-719.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rasheed MU, Thajuddin N, Ahamed P, Teklemariam Z, Jamil K (2014) Antimicrobial drug resistance in strains of Escherichia coli isolated from food sources. Rev Inst Med Trop Sao Paulo 56:341–346. https://doi.org/10.1590/S0036-46652014000400012

    Article  PubMed  PubMed Central  Google Scholar 

  13. Russo TA, Johnson JR (2000) A proposal for an inclusive designation for extraintestinal pathogenic Escherichia coli: ExPEC. J Infect Dis 181:1753–1754. https://doi.org/10.1086/315418

    Article  CAS  PubMed  Google Scholar 

  14. Banatvala N, Griffin PM, Greene KD, Barrett TJ, Bibb WF, Green JH et al (2001) The United States national prospective hemolytic uremic syndrome study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis 183:1063–1070. https://doi.org/10.1086/319269

    Article  CAS  PubMed  Google Scholar 

  15. Albert MJ, Faruque SM, Faruque AS, Neogi PK, Ansaruzzaman M, Bhuiyan NA, Alam K, Akbar MS (1995) Controlled study of Escherichia coli diarrheal infections in Bangladeshi children. J Clin Microbiol 33:973–977. https://doi.org/10.1128/jcm.33.4.973-977.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Meena R, Amee RM, Chitrita D, Sherry PS, James RJ, Lee WR (2005) Possible animal origin of human-associated, multidrug-resistant, uropathogenic Escherichia coli. Clin Infect Dis 40:251–257. https://doi.org/10.1086/426819

    Article  Google Scholar 

  17. Van Andel T, De Boer HJ, Barnes J, Vandebroek I (2014) Medicinal plants used for menstrual disorders in Latin America, the Caribbean, sub-Saharan Africa, South and Southeast Asia and their uterine properties. J Ethnopharmacol 155:992–1000. https://doi.org/10.1016/j.jep.2014.06.049

    Article  PubMed  Google Scholar 

  18. Dorman HJD, Deans SG (2000) Antimicrobial agents from plants: antibacterial activity of plant volatile oil. J Appl Microbiol 88:308–316. https://doi.org/10.1046/j.1365-2672.2000.00969.x

    Article  CAS  PubMed  Google Scholar 

  19. Ozawa T, Lilley TH, Haslam E (1987) Polyphenol interactions: astringency and the loss of astringency in ripening fruit. Phytochem Lett 26:2937–2942. https://doi.org/10.1016/S0031-9422(00)84566-5

    Article  CAS  Google Scholar 

  20. Abdessadak O, Hajji H, Koubi Y, Lakhlifi T, Ajana MA, Bouachrine M (2021) Study of dipolar 1.3 cycloaddition reaction by DFT method, as well as a study of antibacterial activity of two isomers 1.4 and 1.5 on two therapeutic targets E. coli and Helicobacter pylori, by molecular docking. Turkish Comp Theo Chem 4:46–55. https://doi.org/10.33435/tcandtc.1020278

  21. Skowron EA, Friedlander ML (2009) The differentiation of self inventory: development and initial validation. J Couns Psychol 56:597–598. https://doi.org/10.1037/a0016709

    Article  Google Scholar 

  22. Wiederstein M, Manfred JS (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids Res 35:407–410. https://doi.org/10.1093/nar/gkm290

    Article  Google Scholar 

  23. Lokhande KB, Banerjee T, Swamy KV, Ghosh P, Deshpande M (2022) An in silico scientific basis for LL-37 as a therapeutic for COVID-19. Proteins 5(90):1029–1043. https://doi.org/10.1002/prot.26198

    Article  CAS  Google Scholar 

  24. Mansuri A, Lokhande K, Kore S, Gaikwad S, Nawani N, Swamy KV, Junnarkar M, Pawar S (2020) Antioxidant, anti-quorum sensing, biofilm inhibitory activities and chemical composition of Patchouli essential oil: in vitro and in silico approach. J Biomol Struct Dyn 1(40):154–165. https://doi.org/10.1080/07391102.2020.1810124

    Article  CAS  Google Scholar 

  25. El-khatabi K, Aanouz I, Aouidate A, Ghaleb A, Ajana MA, Bouachrine M, Lakhlifi T (2019) Discovery of new Sulfur-containing 1, 4-naphthoquinone oxime derivatives as anti-MDR cancer agents using 3D QSAR and docking methods, RHAZES: Green and Applied Chemistry 7:45–56. https://doi.org/10.48419/IMIST.PRSM/rhazes-v7.18386

  26. Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:1–13. https://doi.org/10.1038/srep42717

    Article  Google Scholar 

  27. Gupta RK, Apte GR, Lokhande KB, Mishra S, Pal JK (2020) Carbohydrate-binding agents: potential of repurposing for COVID-19 therapy. Curr Protein Pept Sci 11(21):1085–1096. https://doi.org/10.2174/1389203721666200918153717

  28. Lokhande KB, Ghosh P, Nagar S et al (2022) Novel B, C-ring truncated deguelin derivatives reveals as potential inhibitors of cyclin D1 and cyclin E using molecular docking and molecular dynamic simulation. Mol Divers 26:2295–2309. https://doi.org/10.1007/s11030-021-10334-z

    Article  CAS  PubMed  Google Scholar 

  29. Pulakuntla S, Lokhande KB, Padmavathi P et al (2021) Mutational analysis in international isolates and drug repurposing against SARS-CoV-2 spike protein: molecular docking and simulation approach. Virus Dis 32:690–702. https://doi.org/10.1007/s13337-021-00720-4

    Article  CAS  Google Scholar 

  30. Belhassan A, Zaki H, Chtita S, Alaqarbeh M, Alsakhen N, Benlyas M, Lakhlifi T, Bouachrine M (2021) Camphor, artemisinin and sumac phytochemicals as inhibitors against COVID-19: Computational approach. Comput Biol Med 136:104758. https://doi.org/10.1016/j.compbiomed.2021.104758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Belhassan A, Chtita S, Zaki H, Alaqarbeh M, Alsakhen N, Almohtaseb F, Lakhlifi T, Bouachrine M (2022) In silico detection of potential inhibitors from vitamins and their derivatives compounds against SARS-CoV-2 main protease by using molecular docking, molecular dynamic simulation and ADMET profiling. J Mol Struct 1258:132652. https://doi.org/10.1016/j.molstruc.2022.132652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors express their gratitude to the “Association Marcaine des chimistes théoriciens” (AMCT) for technical support.

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Authors and Affiliations

  1. Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Meknes, Morocco

    Oumayma Abdessadak, Mohammed Aziz Ajana, Tahar Lakhlifi & Mohammed Bouachrine

  2. National Agricultural Research Center, Al-Baqa, 19381, Jordan

    Marwa Alaqarbeh

  3. Ministry of Water and Irrigation, Laboratory and Quality Affairs, Amman, Jordan

    Firas Almohtaseb

  4. The Hashemite University, Zarqa, Jordan

    Nada Alsakhen

  5. EST Khenifra, Sultan Moulay Sliman University, Benimellal, Morocco

    Mohammed Bouachrine

  6. 3BIO Laboratory, EST Khenifra, Sultan Moulay Slimane University, Beni Mellal, Morocco

    Hanane Zaki

Authors
  1. Oumayma Abdessadak
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  2. Marwa Alaqarbeh
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  3. Hanane Zaki
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  4. Firas Almohtaseb
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  6. Mohammed Aziz Ajana
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  7. Tahar Lakhlifi
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Contributions

Data collection, material preparation, analysis, and writing were conducted by Abdessadak O; material and analysis of MD simulation and study justification by Alaqarbeh M; analysis by Zaki H; Almohtaseb F and Alsakhen N; data analysis, study justification, and supervision by Ajana M A; supervision and project administration by Lakhlifi T; and study justification and supervision by Bouachrine M.

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Correspondence to Marwa Alaqarbeh.

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Abdessadak, O., Alaqarbeh, M., Zaki, H. et al. Computational approaches to discover a Kaempferol derivative extracted from Senna alexandrina as Escherichia coli enzyme (MurF) inhibitor by molecular docking, molecular dynamics simulation, and ADME-Tox. Struct Chem 34, 1173–1187 (2023). https://doi.org/10.1007/s11224-022-02068-x

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