Modern Chemistry

| Peer-Reviewed |

Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2)

Received: Dec. 04, 2022    Accepted: Dec. 29, 2022    Published: Feb. 06, 2023
Views:       Downloads:

Share

Abstract

Nicotinamide Adenine Dinucleotide Hydrogen (NADH)-ubiquinone oxidoreductase in Plasmodium falciparum (PfNDH2) constitute a feasible target for anti-malarial drug discovery. This work aims at investigating the inhibitory activities of selected phytochemicals in Artemisia Afra against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum. 50 phytochemicals were selected based on structural stability. Quantum mechanical Density Functional Theory (DFT) studies with B3LYP at 6-311G* level was done on pfNDH2 as the apoprotein control. Pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking was used to study the PfNDH2 inhibiting activities of the 50 compounds from Artemisia afra. Out of these 50 phytochemicals, 2,4,6-Triphenyl-1,3 dioxane (2,4,6 TPD), chamazulene, aromadendrene, 1-epi-bBicyclosesquiphellandrene (1-EBSP) and cis-muurola-3,5-diene (CM3,5D) passed the physicochemical properties of the Lipinski rule of 5, binding mode, molecular interaction and ADMET calculations. These five compounds also showed high binding affinity of -8.9 kJ/mol, -7.7kJ/mol, -7.3kJ/mol, -7.1kJ/mol and -7.1kJ/mol at the binding pores of PfNDH2 respectively. The reactivity of these compounds was also investigated by the electron donating and accepting activities of the compounds using Density Functional Theory calculated Higher Occupied Molecular Orbital, Lower Unoccupied Molecular Orbital energy and HOMO/LUMO energy gap revealed the stability of the compounds due to the low energy gap values obtained. The values obtained showed that aromadendrene and chamazulene were potential inhibitors of PfNDH2 and were the most potent and therefore, recommended for therapeutic efficacy investigation.

DOI 10.11648/j.mc.20231101.12
Published in Modern Chemistry ( Volume 11, Issue 1, March 2023 )
Page(s) 23-33
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Molecular Docking, Artemisia Afra, Plasmodium Falciparum, Phytochemicals

References
[1] Anneke du Toit and Frank van der Kooy (2019) Artemisia afra, a controversial herbal remedy or a treasure trove of new drugs? Journal of Ethnopharmacol. doi: 10.1016/j.jep.2019.112127 Vol244 15 112 -127
[2] Ian E. Cock and Sandy F. Van Vuuren (2020) The traditional use of southern African medicinal plants in the treatment of viral respiratory diseases: A review of the ethnobotany and scientific evaluations, journal of Ethnopharmacol. 262: 113194. doi: 10.1016/j.jep.2020.113194
[3] Adejoro I. A., Waheed S. O., Adeboye O. O. (2016) Molecular Docking Studies of Lonchocarpus cyanescens Triterpenoids as Inhibitors for Malaria. J Phys Chem Biophys 6: 213. doi: 10.4172/2161-0398.1000213
[4] Paul D Lyne (2002) Structural base virtual screening: An overview Drug Discovery Today Volume 7, Issue 20, Pages 1047-1055.
[5] Cheng F, Li W, Zhou Y, et al (2012) admetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET Properties. J Chem Inf Model 52 (11): 3099-3105. https://doi.org/10.1021/ci300367a
[6] Md. Anayet Hasan, Md. Habibul Hasan Mazumder, Afrin Sultana Chowdhury, Amit Datta and Md. Arif Khan (2015) Molecular-docking study of malaria drug target enzyme transketolase in Plasmodium falciparum 3D7 portends the novel approach to its treatment Source Code for Biology and Medicine 10: 7 2-14 DOI 10.1186/s13029-015-0037-3
[7] Chandrajit Dohutia1, Dipak Chetia, Kabita Gogoi, Dibya Ranjan Bhattacharyya, Kishore Sarma (2017) Molecular docking, synthesis and in vitro antimalarial evaluation of certain novel curcumin analogues. Brazilian Journal of Pharmaceutical Sciences http://dx.doi.org/10.1590/s2175-97902017000400084
[8] Anna Jaromin, Beata Gryzio, Marek Jamrozik, Silvia Parapini, Nicoletta Basilico, Marek Cegia, Donatella Taramelli and Agnieszka Zagorska (2021) Synthesis, Molecular Docking and Antiplasmodial Activities of New Tetrahydro-β-Carbolines Int. J. Mol. Sci. 22 (24), 13569; https://doi.org/10.3390/ijms222413569
[9] Akinwunmi O. Adeoye a, c,*, John O. Olanlokun b, Habib Tijani c, Segun O. Lawal b, Cecilia O. Babarinde b, Mobolaji T. Akinwole b, Clement O. Bewaji c (2019). Molecular docking analysis of apigenin and quercetin from ethylacetate fraction of Adansonia digitata with malaria-associated calcium transport protein: An in silico approach. volume 5, Issue 9, E02248 https://doi.org/10.1016/j.heliyon..e02248
[10] Zaharaddeen Shehu, A. Uzairu an Balarabe S. Sagagi (2018) Quantitative Structure Activity Relationship (QSAR) and Molecular Docking Study of Some Pyrrolones Antimalarial Agents against Plasmodium Falciparum. 1-17DOI: 10.18596/jotcsa.346661
[11] Hanine Hadni and Menana Elhallaoui (2019) Molecular docking and QSAR studies for modeling the antimalarial activity of hybrids 4-anilinoquinoline-triazines derivatives with the wild-type and mutant receptor pf-DHFR. Heliyon Vol. Issue 8 https://doi.org/10.1016/j.heliyon.e02357.
[12] Shehu Z, Uzairu A, Sagagi B. (2018) Quantitative Structure-Activity Relationship and Molecular Docking Study of Some Pyrrolones Antimalarial Agents against Plasmodium Falciparum. JOTCSA.; 5 (2): 569–84. DOI: http://dx.doi.org/10.18596/jotcsa.346661.
[13] Isaiah A. Adejoro, Sodiq O. Waheed Omolara O. Adeboye, Frederick U. Akhigbe (2017). Molecular Docking of the Inhibitory Activities of Triterpenoids of Lonchocharpus cyanescens against Ulcer. Journal of Biophysical Chemistry: 8,1-11. https://doi.org/10.4236/jbpc.2017.81001.
[14] Olawale F. Akinyele, Emmanuel G. Fakola, Oluwatoba E. Oyeneyin. Omolara O. Adeboye, Ayowole O. Ayeni, Justinah S. Amoko and Temitope A. Ajayeoba (2020) Molecular Docking Study of Primaquine-Favipiravir Based Compounds as Potential Inhibitors of COVID-19 Main Protease. European Reviews of Chemical Research, 2020, 7 (1) 3-15DOI: 10.13187/ercr.2020.1.3
[15] O. O. Adeboye, F. O. Oyeleke, S. A. Agboluaje, Molecular Docking of Inhibitory Activities of Syzygium Cordatum against Mycobacterium Tuberculosis, Adv. J. Chem. A, 2022, 5 (2), 147-163. DOI: 10.22034/AJCA.2022.310927.1286 URL: http://www.ajchem-a.com/article_146908.htm
[16] Shyamalambica P, Tapas Ranjan Samal, Mavuduri Jagannath (2019) Molecular-Docking Studies of Malaria Drug Target Enzyme Nad – Dependant Protein Deacylases Sir2a in Plasmodium Falciparum – A Novel Approach to its treatment. Research Journal Life Sciences, Bioinformatics, Pharmaceutical and Chemical Sciences 5 (1) 243 – 261. DOI: 10.26479/2019.0501.2
[17] Kim S. Han L. Yu B. Hähnke V. D. Bolton E. E. Bryant S. H. (2016) PubChem structure-activity relationship (SAR) clusters J Cheminform 7 33 Pubchem (https://pubchem.ncbi.nlm.nih.gov/
[18] protein data bank RCSB (http://www.rcsb.org/pdb)
[19] BIOVIA, Discovery Studio Software Dassault Systèmes, [19.1], San Diego: Dassault Systèmes, [2019].
[20] Yang Y, Yu Y, Li X, Li J, Wu Y, Yu J, Ge J, Huang Z, Jiang L, Rao Y, Yang M (2017). Target Elucidation by Cocrystal Structures of NADH-Ubiquinone Oxidoreductase of Plasmodium falciparum (PfNDH2) with Small Molecule To Eliminate Drug-Resistant Malaria. J Med Chem. 9; 60 (5): 1994-2005. doi: 10.1021/acs.jmedchem.6b01733. Epub. PMID: 28195463.
[21] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. and Olson, A. J. (2009) AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexiblity. Journal of Computational Chemistry, 30, 2785-2791. http://dx.doi.org/10.1002/jcc.21256
[22] H. Yang, C. Lou, L. Sun, J. Li, Y. Cai, Z. Wang, W. Li, G. Liu, Y. Tang (2019), (https://lmmd.ecust.edu.cn/admetsar2/).
[23] (https://molinspiration.com)
[24] Lipinski CA. Lead profiling Lead- and drug-like compounds : the rule-of-five revolution. Drug Discovery Today. 2004; 1 (4): 337-341. doi: 10.1016/j.ddtec.2004.11.007
[25] Tsaioun K, Kates SA (2010) ADMET for Medicinal Chemists: A Practical Guide. John Wiley and Sons, Singapore 145-200. https://doi.org/ 10.1002/9780470915110
[26] Hughes J. P., Rees S, Kalindjian SB, Philpott KL (2011) Principles of early drug. Br J Pharmacol 162: 1239-1249. https://doi.org/10.1111/j.1476-5381.2010.01127.x
[27] Stevens E (2014) Lead Discovery. In: Jaworski A (ed) Medicinal Chemistry: Modern Drug Discovery Process. Pearson, pp 247–272.
[28] Mccarren P, Springer C, Whitehead L (2011) An investigation into pharmaceutically relevant mutagenicity data and the influence on Ames predictive potential. J Cheminform 3 (51): 1-20. https://doi.org/10.1186/1758-2946-3-51
[29] Hopkins AL, Keserü GM, Leeson PD, et al (2014) The role of ligand efficiency metrics in drug discovery. Nat Rev Drug Discov 13 (2): 105-121. https://doi.org/10.1038/nrd4163
[30] Heßelmann A. DFT-SAPT Intermolecular Interaction Energies Employing Exact-Exchange Kohn-Sham Response Methods. J Chem Theory Comput. 2018 Apr 10; 14 (4): 1943-1959. doi: 10.1021/acs.jctc.7b01233. Epub 2018 Apr 2. PMID: 29566325.
Cite This Article
  • APA Style

    Omolara Olubunmi Adeboye, Sunday Olawale Okeniyi, Saheed Alabi Agboluaje, Francis Oretayo Oyeleke, Olawale Folorunso Akinyele. (2023). Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2). Modern Chemistry, 11(1), 23-33. https://doi.org/10.11648/j.mc.20231101.12

    Copy | Download

    ACS Style

    Omolara Olubunmi Adeboye; Sunday Olawale Okeniyi; Saheed Alabi Agboluaje; Francis Oretayo Oyeleke; Olawale Folorunso Akinyele. Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2). Mod. Chem. 2023, 11(1), 23-33. doi: 10.11648/j.mc.20231101.12

    Copy | Download

    AMA Style

    Omolara Olubunmi Adeboye, Sunday Olawale Okeniyi, Saheed Alabi Agboluaje, Francis Oretayo Oyeleke, Olawale Folorunso Akinyele. Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2). Mod Chem. 2023;11(1):23-33. doi: 10.11648/j.mc.20231101.12

    Copy | Download

  • @article{10.11648/j.mc.20231101.12,
      author = {Omolara Olubunmi Adeboye and Sunday Olawale Okeniyi and Saheed Alabi Agboluaje and Francis Oretayo Oyeleke and Olawale Folorunso Akinyele},
      title = {Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2)},
      journal = {Modern Chemistry},
      volume = {11},
      number = {1},
      pages = {23-33},
      doi = {10.11648/j.mc.20231101.12},
      url = {https://doi.org/10.11648/j.mc.20231101.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.mc.20231101.12},
      abstract = {Nicotinamide Adenine Dinucleotide Hydrogen (NADH)-ubiquinone oxidoreductase in Plasmodium falciparum (PfNDH2) constitute a feasible target for anti-malarial drug discovery. This work aims at investigating the inhibitory activities of selected phytochemicals in Artemisia Afra against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum. 50 phytochemicals were selected based on structural stability. Quantum mechanical Density Functional Theory (DFT) studies with B3LYP at 6-311G* level was done on pfNDH2 as the apoprotein control. Pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking was used to study the PfNDH2 inhibiting activities of the 50 compounds from Artemisia afra. Out of these 50 phytochemicals, 2,4,6-Triphenyl-1,3 dioxane (2,4,6 TPD), chamazulene, aromadendrene, 1-epi-bBicyclosesquiphellandrene (1-EBSP) and cis-muurola-3,5-diene (CM3,5D) passed the physicochemical properties of the Lipinski rule of 5, binding mode, molecular interaction and ADMET calculations. These five compounds also showed high binding affinity of -8.9 kJ/mol, -7.7kJ/mol, -7.3kJ/mol, -7.1kJ/mol and -7.1kJ/mol at the binding pores of PfNDH2 respectively. The reactivity of these compounds was also investigated by the electron donating and accepting activities of the compounds using Density Functional Theory calculated Higher Occupied Molecular Orbital, Lower Unoccupied Molecular Orbital energy and HOMO/LUMO energy gap revealed the stability of the compounds due to the low energy gap values obtained. The values obtained showed that aromadendrene and chamazulene were potential inhibitors of PfNDH2 and were the most potent and therefore, recommended for therapeutic efficacy investigation.},
     year = {2023}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Molecular Docking of the Inhibitory Activities of Selected Phytochemicals in Artemisia Afra Against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum (PfNDH2)
    AU  - Omolara Olubunmi Adeboye
    AU  - Sunday Olawale Okeniyi
    AU  - Saheed Alabi Agboluaje
    AU  - Francis Oretayo Oyeleke
    AU  - Olawale Folorunso Akinyele
    Y1  - 2023/02/06
    PY  - 2023
    N1  - https://doi.org/10.11648/j.mc.20231101.12
    DO  - 10.11648/j.mc.20231101.12
    T2  - Modern Chemistry
    JF  - Modern Chemistry
    JO  - Modern Chemistry
    SP  - 23
    EP  - 33
    PB  - Science Publishing Group
    SN  - 2329-180X
    UR  - https://doi.org/10.11648/j.mc.20231101.12
    AB  - Nicotinamide Adenine Dinucleotide Hydrogen (NADH)-ubiquinone oxidoreductase in Plasmodium falciparum (PfNDH2) constitute a feasible target for anti-malarial drug discovery. This work aims at investigating the inhibitory activities of selected phytochemicals in Artemisia Afra against NADH-Ubiquinone Oxidoreductase of Plasmodium Falciparum. 50 phytochemicals were selected based on structural stability. Quantum mechanical Density Functional Theory (DFT) studies with B3LYP at 6-311G* level was done on pfNDH2 as the apoprotein control. Pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking was used to study the PfNDH2 inhibiting activities of the 50 compounds from Artemisia afra. Out of these 50 phytochemicals, 2,4,6-Triphenyl-1,3 dioxane (2,4,6 TPD), chamazulene, aromadendrene, 1-epi-bBicyclosesquiphellandrene (1-EBSP) and cis-muurola-3,5-diene (CM3,5D) passed the physicochemical properties of the Lipinski rule of 5, binding mode, molecular interaction and ADMET calculations. These five compounds also showed high binding affinity of -8.9 kJ/mol, -7.7kJ/mol, -7.3kJ/mol, -7.1kJ/mol and -7.1kJ/mol at the binding pores of PfNDH2 respectively. The reactivity of these compounds was also investigated by the electron donating and accepting activities of the compounds using Density Functional Theory calculated Higher Occupied Molecular Orbital, Lower Unoccupied Molecular Orbital energy and HOMO/LUMO energy gap revealed the stability of the compounds due to the low energy gap values obtained. The values obtained showed that aromadendrene and chamazulene were potential inhibitors of PfNDH2 and were the most potent and therefore, recommended for therapeutic efficacy investigation.
    VL  - 11
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Chemistry, Emmanuel Alayande College of Education, Oyo, Nigeria

  • Department of Chemistry, Nigerian Defence Academy, Kaduna, Nigeria

  • Department of Chemistry, Nigerian Defence Academy, Kaduna, Nigeria

  • Department of Chemistry, Ekiti State University, Ado Ekiti, Nigeria

  • Department of Chemistry, Obafemi Awolowo University, Ile-Ife, Nigeria

  • Section