Elhafnaoui LANEZ, Touhami LANEZ, Nadjiba ZEGHEB

404121

In silico ADMET, toxicological analysis, molecular docking studies and Molecular dynamics simulation of Afzelin with potential antibacterial effects against Staphylococcus aureus

In silico ADMET, toxicological analysis, molecular docking studies and Molecular dynamics simulation of Afzelin with potential antibacterial effects against Staphylococcus aureus

Afzelin has been designed and tested for its in silico antibacterial activity against DNA gyrase complex of Staphyloccocus aureus. The results of the toxicity study indicate that afzelin displayed moderate antibacterial potential against staphylococcus aureus with LD50 = 5000 mg/Kg, which is almost four times and a half weaker than that obtained for the commercial antibiotic chloramphenicol. The afzelin and the commercial antibiotic chloramphenicol were subjected to docking studies to understand their interaction with DNA gyrase complex of Staphyloccocus aureus. Results indicated a good affinity of afzelin to the chosen target with the formation of four hydrogen bonds and binding energy of 29.82 KJ/mol. ADME study shows that afzelin is not inhibitors of CYP450 IA2, 2C19, 2C9, 2D6, 3A4 isoenzymes which suggests a decrease in their plasma concentrations and a rapid elimination route. Molecular dynamics simulations were performed for 10 ns for afzelin using the gromacs package to assess the conformational stability of protein-ligand complexes during the simulation.
Keywords:

Euphorbia falcata L binding energy, antibacterial activity, afzelin,

PDF

___

  • [1] V.M. D’Costa, C.E. King, L. Kalan, M. Morar, W.W.L. Sung, C. Schwarz, D. Froese, G. Zazula, F. Calmels, R. Debruyne, Antibiotic resistance is ancient, Nature 477 (2011) 457–461.
  • [2] K. Bhullar, N. Waglechner, A. Pawlowski, K. Koteva, E.D. Banks, M.D. Johnston, H.A. Barton, G.D. Wright, Antibiotic resistance is prevalent in an isolated cave microbiome, PLoS One 7 (2012) e34953- e34953.
  • [3] S.Y. Lee, Y.J. So, M.S. Shin, J.Y. Cho, J. Lee, Antibacterial Effects of Afzelin Isolated from Cornus macrophylla on Pseudomonas aeruginosa, A Leading Cause of Illness in Immunocompromised Individuals, Molecules 19 (2014) 3173-3180.
  • [4] J. Wang, A.M. Sci, M. Cao, B. Fan, T. Zhen, A pre-clinical trial study on afzelin: anti-human lung cancer, anti-cholinesterase, and anti-glucosidase properties, Archives of Medical Science (2021) 1-9.
  • [5] K. Shingnaisui, T. Dey, P. Manna, J. Kalita, Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A review, J Ethnopharmacology 220 (2018) 35–43.
  • [6] B.M. Radu, F.B. Epureanu, M. Radu, P.F. Fabene, G. Bertini, Nonsteroidal anti-inflammatory drugs in clinical and experimental epilepsy, Epilepsy Research 131 (2017) 15–27.
  • [7] D.G. Lee, J.S. Lee, N.G. Quilantang, S.D. Jacinto, S. Lee, Determination of Afzelin and Astragalin from Lespedeza cuneata on Aldose Reductase Inhibition, Journal of chromatographic science 59 (2021) 381–387.
  • [8] K.C. Zhu, J.M. Sun, J.G. Shen, J.Z. Jin, F. Liu, X.L. Xu, L. Chen, L.T. Liu, J.J. Lv, Afzelin exhibits anti-cancer activity against androgen-sensitive LNCaP and androgen-independent PC-3 prostate cancer cells through the inhibition of LIM domain kinase 1, Oncology Letters 10 (2015) 2359–2365.
  • [9] I. Radziejewska, K. Supruniuk, R. Czarnomysy, K. Buzun, A. Bielawska, Anti-Cancer Potential of Afzelin towards AGS Gastric Cancer Cells, Pharmaceuticals (Basel), 14 (2021) 1-16.
  • [10] D. Utepbergenov, U. Derewenda, N. Olekhnovich, G. Szukalska, B. Banerjee, M.K. Hilinski, D.A. Lannigan, P.T. Stukenberg, Z.S. Derewenda, Insights into the inhibition of the p90 ribosomal S6 kinase (RSK) by the flavonol glycoside SL0101 from the 1.5 Å crystal structure of the N-terminal domain of RSK2 with bound inhibitor, Biochemistry 51 (2012) 6499–6510.
  • [11] S. Kumar, A.K. Pandey, Chemistry and biological activities of flavonoids: An overview, The Scientific World Journal 2013 (2013) 1-16.
  • [12] F.M. Afendi, T. Okada, M. Yamazaki, A. Hirai-Morita, Y. Nakamura, K. Nakamura, S. Ikeda, H. Takahashi, M. Altaf-Ul-Amin, L.K. Darusman, K. Saito, S. Kanaya, KNApSAcK family databases: integrated metabolite-plant species databases for multifaceted plant research, Plant and Cell Physiology 53 (2012) 1-12.
  • [13] E. Rachmi, B.B. Purnomo, A.T. Endharti, L.E. Fitri, Identification of afzelin potential targets in inhibiting triple-negative breast cancer cell migration using reverse docking, Porto Biomedical Journal 5 (2020) 1-8.
  • [14] H. Lade, J.S. Kim, Bacterial targets of antibiotics in methicillin-resistant staphylococcus aureus, Antibiotics 10 (2021) 1-29.
  • [15] D.J. Dwyer, M.A. Kohanski, B. Hayete, J.J. Collins, Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli, Molecular Systems Biology 3 (2007) 1-15.
  • [16] A.Y.C. Saiki, L.L. Shen, C.-M. Chen, J. Baranowski, C.G. Lerner, DNA Cleavage Activities of Staphylococcus aureus Gyrase and Topoisomerase IV Stimulated by Quinolones and 2-Pyridones, Antimicrobial Agents and Chemotherapy 43 (1999) 1574-1577.
  • [17] S. Gottschalk, D. Ifrah, S. Lerche, C.T. Gottlieb, M.T. Cohn, H. Hiasa, P.R. Hansen, L. Gram, H. Ingmer, L.E. Thomsen, the antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus, BMC Microbiology 13 (2013) 1-8.
  • [18] M. Ouassaf, S. Belaidi, S. Chtita, T. Lanez, F. Abul Qais, H. Md Amiruddin. Combined molecular docking and dynamics simulations studies of natural compounds as potent inhibitors against SARS-CoV-2 main protease, Journal of Biomolecular Structure and Dynamics 40 (2022) 11264-11273.
  • [19] B.A. Sherer, K. Hull, O. Green, G. Basarab, S. Hauck, P. Hill, J.T. Loch, G. Mullen, S. Bist, J. Bryant, A. Boriack-Sjodin, J. Read, N. Degrace, M. Uria-Nickelsen, R.N. Illingworth, A.E. Eakin, Pyrrolamide DNA gyrase inhibitors: Optimization of antibacterial activity and efficacy, Bioorganic Medicinal Chemistry Letters 21 (2011) 7416–7420.
  • [20] L. Drago, Chloramphenicol resurrected: A journey from antibiotic resistance in eye infections to biofilm and ocular microbiota, Microorganisms 7 (2019) 1-12.
  • [21] A.C.R. Silvino, G.L. Costa, F.C.F. De Araújo, D.B. Ascher, D.E.V. Pires, C.J.F. Fontes, L.H. Carvalho, C.F.A. De Brito, T.N. Sousa, Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses, PLoS One 11 (2016) 1-14.
  • [22] T. Eitrich, A. Kless, C. Druska, W. Meyer, J. Grotendorst, Classification of highly unbalanced CYP450 data of drugs using cost sensitive machine learning techniques, J of Chemical Information and Modeling 47 (2007) 92–103.
  • [23] M. Louet, C.M. Labbé, C. Fagnen, C.M. Aono, P. Homem-de-Mello, B.O. Villoutreix, M.A. Miteva, Insights into molecular mechanisms of drug metabolism dysfunction of human CYP2C9*30, PLoS One 13 (2018) 1-21.
  • [24] R.A. Terkeltaub, D.E. Furst, J.L. Digiacinto, K.A. Kook, M.W. Davis, Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors, Arthritis and Rheumatology 63 (2011) 2226–2237.
  • [25] A. Zahno, K. Brecht, R. Morand, S. Maseneni, M. Török, P.W. Lindinger, S. Krähenbühl, The role of CYP3A4 in amiodarone-associated toxicity on HepG2 cells, Biochemical Pharmacology 81 (2011) 432–441.
  • [26] M.N. Drwal, P. Banerjee, M. Dunkel, M.R. Wettig, R. Preissner, ProTox: a web server for the in-silico prediction of rodent oral toxicity, Nucleic Acids Research 42 (2014) W53–W58.
Turkish Computational and Theoretical Chemistry-Cover
  • ISSN: 2587-1722
  • Başlangıç: 2017
  • Yayıncı: Koray SAYIN
Arşiv
Sayıdaki Diğer Makaleler

Mimic toxicity of Beta-blocker drugs by structural base descriptors

Akshay TİWARİ

Structural, Spectral, Antibacterial and Anticancer Investigations of Synthesized Isoxazole Derivatives

Elif GÜNEY, Koray SAYİN

Simple model for the calculation of concentration and temperature dependent refractive index of different solutions

Umar FAROOQUE, Sandhir Kumar SİNGH, Tarique RASHİD, Md. Iftekhar ALAM

In silico ADMET, toxicological analysis, molecular docking studies and Molecular dynamics simulation of Afzelin with potential antibacterial effects against Staphylococcus aureus

Elhafnaoui LANEZ, Touhami LANEZ, Nadjiba ZEGHEB

Influence of electronic structure of (R)-4-menten-3-one on its restricted rotation and inversion

Ivan VAKULİN, Elvira LATYPOVA, Rifkat FAATOVİCH, Gumer Yusupovich ISHMURATOV, Guzel Rafailovna TALIPOVA

Could Zingiber officinale plant be effective against Omicron BA.2.75 of SARS-CoV-2?

Handan SARAÇ, Ahmet DEMİRBAŞ, Burak TÜZÜN