Molecular Docking, Drug likeness Studies and ADMET prediction of Flavonoids as Platelet-Activating Factor (PAF) Receptor Binding

Document Type : Research Article


1 b p 11201، Avenue Zitoune, Meknes, Morocco

2 Faculty of Science, Moulay Ismail University of Meknes, Morocco

3 Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco

4 EST Khenifra, Sultan Moulay Sliman University, Benimellal, Morocco


Studies and scientific research indicate that the platelet-activating factor (PAF) is a major pro-inflammatory mediator in the initiation and development of cancer. There is also evidence confirming that PAF is an integral part of suppressing the immune system and promoting the appearance of a malignant tumor. For this reason, it is useful to analyze the molecular docking data of eleven flavonoids derivatives isolated from the active leaf extracted from chromolaena odorata with their anti-PAF activity. As a result, it is evident that the natural product of flavonoids may have a positive effect in the development of both therapeutic and preventive agents for platelet activating factor (PAF) antagonist and suggests potential guidelines for the design of PAF inhibitors. Based on the docking score analysis, drug likeness study, and ADMET prediction. We found that six compounds respect all drug-likeness rules and can be used as a potent molecule for inhibition of platelet activating factor (PAF).


Main Subjects

[1]   R. N. Pinckard, A NEW CLASS OF LIPID. J  Biol  Chem. 254 (2020)  9355_9358.
[2]   P. Detopoulou and T. Nomikos, Platelet Activating Factor in Heart Failure : Potential Role in Disease Progression and Novel Target for Therapy,Curr. Heart. Fail. Rep. 10 (2013) 122–129.
[3]   R. Lordan, A. Tsoupras and I. Zabetakis, The Potential Role of Dietary Platelet-Activating Factor Inhibitors in Cancer Prevention and Treatment, Amer.  So.  for Nut.  10 (2019) 148–164.
[4]   V. Melnikova and M. Bar-eli, Inflammation and melanoma growth and metastasis : The role of platelet-activating factor ( PAF ) and its receptor, Cancer Meta. Rev 26 (2009) 359–371.
[5]   V. O. Melnikova and M. Bar-eli, Inflammation and melanoma metastasis, Pigment Cell Melanoma Res. 22 (2007) 257–267.
[6]   L. El Mchichi, A. Belhassan, A. Aouidate, A. Ghaleb, T. Lakhlifi and M. Bouachrine,  QSAR study of new compounds based on 1,2,4-triazole as potential anticancer agents, Phys.  Chem.  Res.  8 (2020) 125–137.
[7]   J. Summers and D. H. Albert, Platelet Activating Factor Antagonists, Adv.  in Pharm. 32(1995).
[8]   V. D. Papakonstantinou, N. Lagopati, E.C. Tsilibary, C. A. Demopoulos and A. I. Philippopoulos, A Review on Platelet Activating Factor Inhibitors : Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties ?, Bioi. Chem and App  2017 (2017) 1_19.
[9]   S. P. Bhatia, D. Mcginty, C. S. Letizia and A. M. Api, Fragrance material review on cedrol, Food and Chem. Tox.  46 (2008)100–102.
[10] H. O. Yang, D. Sal, and B. Ha, Isolation and Characterization of Platelet-Activating Factor Receptor Binding Antagonists from Biota orientalis.Planta Med. 61 (1995).
[11] T. Y. Shen , S. Hwang, N. M. Chang, T. M. Doebber, M. T. Lam, M. S. Wu, X. Wang, G. Q. Han and R. Z. Li, Characterization of a platelet-activating factor receptor antagonist isolated from haifenteng (Piper futokadsura): Specific inhibition of in vitro and in vivo platelet-activating factor-induced effects, Proc. Nati. Acad. Sci. 82 (1985) 672–676.
[12] L. El Mchichi, A. El Aissouq, A. Belhassan, R, El-Mernissi, A. Ouammou, T. Lakhlifi, M. Bouachrine, “Materials Today : Proceedings In silico design of novel Pyrazole derivatives containing thiourea skeleton as anti-cancer agents using : 3D QSAR , Drug-Likeness studies , ADMET prediction and molecular docking,” Mater. Today Proc., 2021, doi: 10.1016/j.matpr.2021.03.152.
[13] A. Adamski, D. Kruszka, Z. Dutkiewicz, M. Kubicki, V. Patroniak and A. Gorczy,  Novel family of fused tricyclic [1, 4] diazepines : Design , synthesis , crystal structures and molecular docking studies,Tetrahedron 73 (2017) 3377–3386.
[14] S. K. Ling, M. M. Pisar and S. Man, Platelet-Activating Factor ( PAF ) Receptor Binding Antagonist Activity of the Methanol Extracts and Isolated Flavonoids from Chromolaena odorata ( L .) KING and ROBINSON, Biol. Pharm. Bull. 30 (2007) 1150–1152.
[15] M. Clark, R. D. Cramer and N. Van Opdenbosch, Validation of the General Purpose Tripos5 . 2 Force Field,J. of  Comp. Chem.  8 (1989) 982–1012.
[16] W. P. Purcell and J. A. Singer, A Brief Review and Table of Semiempirical Parameters Used in the Huckel Molecular Orbital Method, J.  of Chem.  and Eng.  Data 12 (1967) 235_246.
[17] O. Trott and A. J. Olson, Software News and Update AutoDock Vina : Improving the Speed and Accuracy of Docking with a New Scoring Function , Efficient Optimization , and Multithreading,J. of  Comp. Chem. 2 (2009) 456_461.
[18] C. A. Hunter, K. R. Lawson and C. J. Urch, Aromatic interactions.J. Chem. Soc.  2 (2001) 651–669.
[19] DassaultSystemes BIOVIA Discovery Studio Modeling Environment, Release 2017 DassaultSystemes, 2016.
[20] L. El Mchichi, A. Aouidate, F. Z. Chokrafi, A. Ghaleb, T. Lakhlifi and M. Bouachrine,   PREDICTION OF BIOLOGICAL ACTIVITY OF PYRAZOLO [3, 4-B] QUINOLINYL ACITAMIDE BY QSAR RESULTS, RHAZES : Grenn and App.  Chem. 3 (2018) 79–93.
[21] K.Onodera, K. Satou and H. Hirota, Evaluations of Molecular Docking Programs for Virtual Screening, J. Chem. Inf. Model. 47 (2007) 1609–1618.
[22] L.Gregory, C. Warren, A. Webster, A. Capelli, B. Clarke, J. LaLonde, M. H. Lambert, M. Lindvall, N. Nevins, S. F. Semus, S. Senger, G. Tedesco, I. D. Wall, J. M. Woolven, C. E. Peishoff and M. S. Head, A Critical Assessment of Docking Programs and Scoring Functions,J. Med. Chem.  49 (2006) 5912–5931.
[23] A.Daina, O. Michielin and V. Zoete, SwissADME : a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Nat. Publ. Gr.  7 (2016) 1–13.
[24] C. A.Lipinski, F. Lombardo, B. W. Dominy and P. J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery permeability in drug discovery and development settings, Adv. Drug. Deliv. Rev.  23 (1997) 3_25.
[25] A. K.Ghose, V. N. Viswanadhan and J. J. Wendoloski, A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases,J. Comb. Chem. 1 (1999) 55–68.
[26] D. F.Veber, S. R. Johnson, H. Cheng, B. R. Smith, K. W. Ward and K. D. Kopple,  Molecular Properties That Influence the Oral Bioavailability of Drug Candidates, J. Med. Chem. 45 (2002) 2615–2623.
[27] W. J.Egan, K. M. Merz and J. J. Baldwin, Prediction of Drug Absorption Using Multivariate Statistics, J. Med. Chem. 43 (2000) 3867–3877.
[28] I.Muegge, S. L. Heald and D. Brittelli, Simple Selection Criteria for Drug-like Chemical Matter, Amer. Chem. soc. 44 (2001)1842_1846.
[29] Y. C.Martin and A. Park, Bioavailability Score, J. Med. Chem. 48 (2005) 3164–3170.
[30] D. E.Pires V, T. L. Blundell and D. B. Ascher, pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures.J Med. Chem. 58 (2015) 4066−4072.
[31]         L. Elmchichi, A. Belhassan, T. Lakhlifi, and M. Bouachrine, 3D-QSAR Study of the Chalcone Derivatives as Anticancer Agents, 2020 (2020).