Document Type : Original Research Article

Author

Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, Iraq

Abstract

A new series of 3-furan-2-yl-1-p-aryl-propenone derivatives containing imine moieties (1-7) were synthesized and characterized using spectral analysis. The synthesized derivatives were screened in vitro against several bacterial species, including Acinetobacter baumannii, Klebsiella pneumonia, Pseudomonas aeruginosa (Gram-negative bacteria), and Staphylococcus aureus (Gram-positive bacteria) to study the effect of different imine moieties on the activity of (E)-1-(4-aminophenyl)-3-(furan-2-yl)prop-2-en-1-one, which represent the potent hit against different bacterial species. The synthesized compounds were found to exhibit modest to vigorous activity, especially compounds 1, 4, and 6-7. The minimum inhibitory concentrations (MICs) of compound 1 and 6 against Acinetobacter baumannii and Staphylococcus aureus were determined. The anti-biofilm activity of the potent discovered compounds (1, 4, 6, and 7) against Acinetobacter baumannii and Staphylococcus aureus were also determined. Docking study of the best discovered hits against the active site of glucosamine-6-phosphate synthase, the antimicrobial target enzyme was achieved to explore the interactions of the synthesized hits inside the enzyme residues.

Graphical Abstract

‎Chalcone Derivatives Containing Imine Moieties as New Antibacterial Agents: Synthesis, SAR, Anti-biofilm Activity and Docking study

Keywords

Main Subjects

  1. M. Ni, C.Q. Meng, J.A. Sikorski, Recent advances in therapeutic chalcones, Expert Opin. Ther. Pat. 14 (2004) 1669–1691, https://doi.org/10.1517/ 13543776.14.12.1669
  2. L. Zhuang, W. Zhang, C.Q. Sheng, W.N. Zhang, C.G. Xing, Z.Y. Miao, Chalcone: a privileged structure in medicinal chemistry, Chem. Rev. 117 (2017) 7762–7810, https://doi.org/10.1021/acs.chemrev.7b00020.
  3. Karaman, H. Gezegen, M.B. Gürdere, A. Dingil, M. Ceylan, Screening of biological activities of a series of chalcone derivatives against human pathogenic microorganisms, Chem. Biodivers. 7 (2010) 400–408, https://doi.org/10.1002/cbdv.200900027.
  4. K. Mahapatra, S.K. Bharti, V. Asati, Anti-cancer chalcones: structural and molecular target perspectives, Eur. J. Med. Chem., 98 (2015) 69–114, https://doi. org/10.1016/j.ejmech.2015.05.004.
  5. Zi, A.R. Simoneau, A. Flavokawain, A novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice, Canc. Res. 65 (2005).
  6. Valla, B. Valla, D. Cartier, R. Le Guillou, R. Labia, L. Florent, S. Charneau, J. Schrevel, P. Potier, New syntheses and potential antimalarial activities of new ‘retinoid-like chalcones’, Eur. J. Med. Chem. 41 (2006) 142–146, https://doi.org/ 10.1016/j.ejmech.2005.05.008.
  7. H. Hans, E.M. Guantai, C. Lategan, P.J. Smith, B. Wan, S.G. Franzblau, J. Gut, P. J. Rosenthal, K. Chibale, Synthesis, antimalarial and antitubercular activity of acetylenic chalcones, Bioorg. Med. Chem. Lett 20 (2010) 942–944, https://doi.org/10.1016/j.bmcl.2009.12.062.
  8. L. Cole, S. Hossain, A.M. Cole, O. Phanstiel, Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents, Biorg Med Chem., 24 (2016) 2768–2776, https://doi.org/10.1016/j. bmc.2016.04.045.
  9. ] B.P. Bandgar, S.S. Gawande, Synthesis and biological screening of a combinatorial library of β-chlorovinyl chalcones as anticancer, anti-inflammatory and antimicrobial agents, Biorg Med Chem., 18 (2010) 2060–2065, https://doi.org/1016/j.bmc.2009.12.077.
  10. K. Mahapatra, S.K. Bharti, V. Asati, Anti-cancer chalcones: structural and molecular target perspectives, Eur. J. Med. Chem., 98 (2015) 69–114, https://doi. org/10.1016/j.ejmech.2015.05.004.
  11. Zi, A.R. Simoneau, A. Flavokawain, A novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice, Canc. Res., 65 (2005).
  12. Beceiro, M. Tomás, and G. Bou, “Antimicrobial resistance and virulence: A successful or deleterious association in the bacterial world?,” Clinical Microbiology Reviews, 26 (2013) 185–230. doi: 10.1128/CMR.00059-12.
  13. M. Sivakumar, S. Priya, M. Doble, Synthesis, biological evaluation, mechanism of action and quantitative structure–activity relationship studies of chalcones as antibacterial agents, Chem. Biol. Drug Des. 73 (2009) 403–415, https://doi.org/ 10.1111/j.1747-0285.2009.00793.x.
  14. S. Bhale, S.B. Dongare, U.B. Chanshetti, Synthesis and Antimicrobial screening of Chalcones containing imidazo [1,2-a] pyridine nucleus, Res. J. Chem. Sci. 3 (2013) 38–42.
  15. Mohammad, S.A. Rahaman, M.D. Moinuddin, Synthesis and antimicrobial activity of 1-(2’’,4’’-dichlorophenyl)-3-(substituted aryl)-2-propene-1-ones, Int. J. Life Sci. Biotechnol. Pharma Res. 2 (2012) 82–87.
  16. A.N.Ferraz et al., “Potentiation of antibiotic activity by chalcone (E)-1-(4′-aminophenyl)-3-(furan-2-yl)-prop-2-en-1-one against gram-positive and gram-negative MDR strains,” Microb. Pathog., 148 (2020). doi: 10.1016/j.micpath.2020.104453.
  17. I. Sultan, A.M. Abdula, R.I. Faeq, M. F. Radi, “Synthesis, characterization, and antimicrobial evaluation of new pyrazolines incorporating imine moiety,” in Journal of Physics: Conference Series, 1853 (2021). doi: 10.1088/1742-6596/1853/1/012043.
  18. H.R. Tomi, A. H. R. Al-Daraji, A. M. Abdula, and M. F. Al-Marjani, “Synthesis, antimicrobial and docking study of three novel 2,4,5-triarylimidazole derivatives,” J. Saudi Chem. Soc., 20 (2016) S509–S516. doi: 10.1016/j.jscs.2013.03.004.
  19. L.Mohsen, A. M. Abdula, A. M. Jassim, W. F. Rodhan, and N. B. Ayrim, “New 3,5-disubstituted-4,5-dihydroisoxazole derivatives: Synthesis, antimicrobial, antioxidant and docking study against glucosamine-6-phosphate synthase,” in Journal of Physics: Conference Series, , vol. 1853 (2021). doi: 10.1088/1742-6596/1853/1/012042.
  20. Banerjee,P.M. Shivapriya, P. K. Gautam, K. Misra, A. K. Sahoo, and S. K. Samanta, “A Review on Basic Biology of Bacterial Biofilm Infections and Their Treatments by Nanotechnology-Based Approaches,” Proceedings of the National Academy of Sciences India Section B - Biological Sciences, 90 (2020) 243–259. doi: 10.1007/s40011-018-01065-7.
  21. Qvortrup et al., “Small Molecule Anti-biofilm Agents Developed on the Basis of Mechanistic Understanding of Biofilm Formation,” Frontiers in Chemistry, vol. 7. Frontiers Media S.A., Nov. 01, 2019, doi: 10.3389/fchem.2019.00742.
  22. L.Bearne and C. Blouin, “Inhibition of Escherichia coli Glucosamine-6-phosphate Synthase by Reactive Intermediate Analogues the role of the 2-amino function in catalysis*,” 2000. [Online]. Available: http://www.jbc.org.
  23. E. Abid, A. M. Abdula, M. F. Al Marjani, and Q. M. Abdulhameed, “Synthesis, antimicrobial, antioxidant and docking study of some novel 3,5- disubstituted- 4,5- dihydro- 1H- pyrazoles incorporating imine moiety,” Egypt. J. Chem., 62 (2019) 1139–1149. doi: 10.21608/EJCHEM.2018.5804.1498.
  24. L. Mohsen, A. M. Abdula, and A. M. N. Jassim, “Synthesis, antimicrobial, antioxidant and docking study of novel isoxazoline derivatives,” Acta Pharm. Sci., 56 (2018) 71–83. doi: 10.23893/1307-2080.APS.05619.
  25. Abdalhassan, S. Jabbar, A. J. Khalf, R. Ibrahim, and A. Mutanabbi, “Synthesis, antimicrobial, antioxidant and docking study of novel 2H-1,4-Benzoxazin-3(4H)-One derivatives,” Egypt. J. Chem., 63 (2020) 225–238. doi: 10.21608/ejchem.2019.16920.2030.
  26. Valgas, S. Machado De Souza, ; Elza, F. A. Smânia, and A. Smânia, “screening methods to determine antibacterial activity of natural products,” Brazilian J. Microbiol., 38 (2007) 369–380.
  27. A.Ali, “Prevention of Proteus mirabilis Biofilm by Surfactant Solution,” Egypt. Acad. J. Biol. Sci, 4 (2012) 1–8. [Online]. Available: www.eajbs.eg.net.
  28. A.O’toole and R. Kolter, “Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis.” Mol Microbiol., 28(1998) 449-61. doi: 10.1046/j.1365-2958.1998.00797.x. PMID: 9632250.
  29. H.Ismail, A. M. Abdula, I. H. R. Tomi, A. H. R. Al-Daraji, and Y. Baqi, “Synthesis, Antimicrobial Evaluation and Docking Study of Novel 3,5-Disubstituted-2-Isoxazoline and 1,3,5-Trisubstituted-2-Pyrazoline Derivatives,” Med. Chem. (Los. Angeles)., 17 (2019) 462–473. doi: 10.2174/1573406415666191107121757.
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