Published December 30, 2020 | Version v1
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Synthesis and antimicrobial activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones

Creators

  • 1. National University of Pharmacy
  • 2. V. N. Karazin Kharkiv National University
  • 3. Kharkiv Medical Academy of Postgraduate
  • 4. Ryvu Therapeutics S.A. Henryka

Description

The aim of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity.

Materials and methods. 1Н NMR spectra were recorded on Varian Mercury-200 (200 MHz), 13C NMR spectra were acquired on Bruker Avance 500 1H NMR (500 MHz) and 13C NMR (125 MHz) in DMSO-d6 and CDCl3. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina.

Results and discussion. The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. сoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase.

Conclusions. Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress conditions

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References

  • Singh, L. R., Avula, S. R., Raj, S., Srivastava, A., Palnati, G. R., Tripathi, C. K. M. et. al. (2017). Coumarin–benzimidazole hybrids as a potent antimicrobial agent: synthesis and biological elevation. The Journal of Antibiotics, 70 (9), 954–961. doi: http://doi.org/10.1038/ja.2017.70
  • Fotso, G. W., Ngameni, B., Storr, T. E., Ngadjui, B. T., Mafu, S., Stephenson, G. R. (2020). Synthesis of Novel Stilbene–Coumarin Derivatives and Antifungal Screening of Monotes kerstingii-Specialized Metabolites Against Fusarium oxysporum. Antibiotics, 9 (9), 537. doi: http://doi.org/10.3390/antibiotics9090537
  • Sanduja, M., Gupta, J., Singh, H., Pagare, P. P., Rana, A. (2020). Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents. Journal of Saudi Chemical Society, 24 (2), 251–266. doi: http://doi.org/10.1016/j.jscs.2019.12.001
  • Mahmoud, M. R., El-Shahawi, M. M., Abu El-Azm, F. S., Abdeen, M. (2017). Synthesis and Antimicrobial Activity of Polyfunctionally Substituted Heterocyclic Compounds Derived from 5-Cinnamoylamino-2-Cyanomethyl-1,3,4-Thiadiazole. Journal of Heterocyclic Chemistry, 54 (4), 2352–2359. doi: http://doi.org/10.1002/jhet.2824
  • Reen, F. J., Gutiérrez-Barranquero, J. A., Parages, M. L., O´Gara, F. (2018). Coumarin: a novel player in microbial quorum sensing and biofilm formation inhibition. Applied Microbiology and Biotechnology, 102 (5), 2063–2073. doi: http://doi.org/10.1007/s00253-018-8787-x
  • Yang, L., Li, S., Qin, X., Jiang, G., Chen, J., Li, B. et. al. (2017). Exposure to Umbelliferone Reduces Ralstonia solanacearum Biofilm Formation, Transcription of Type III Secretion System Regulators and Effectors and Virulence on Tobacco. Frontiers in Microbiology, 8. doi: http://doi.org/10.3389/fmicb.2017.01234
  • Zhang, S., Liu, N., Liang, W., Han, Q., Zhang, W., Li, C. (2016). Quorum sensing-disrupting coumarin suppressing virulence phenotypes in Vibrio splendidus. Applied Microbiology and Biotechnology, 101 (8), 3371–3378. doi: http://doi.org/10.1007/s00253-016-8009-3
  • Ojima, Y., Nunogami, S., Taya, M. (2016). Antibiofilm effect of warfarin on biofilm formation of Escherichia coli promoted by antimicrobial treatment. Journal of Global Antimicrobial Resistance, 7, 102–105. doi: http://doi.org/10.1016/j.jgar.2016.08.003
  • Osman, H., Yusufzai, S. K., Khan, M. S., Abd Razik, B. M., Sulaiman, O., Mohamad, S. et. al. (2018). New thiazolyl-coumarin hybrids: Design, synthesis, characterization, X-ray crystal structure, antibacterial and antiviral evaluation. Journal of Molecular Structure, 1166, 147–154. doi: http://doi.org/10.1016/j.molstruc.2018.04.031
  • Arshad, A., Osman, H., Bagley, M. C., Lam, C. K., Mohamad, S., Zahariluddin, A. S. M. (2011). Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives. European Journal of Medicinal Chemistry, 46 (9), 3788–3794. doi: http://doi.org/10.1016/j.ejmech.2011.05.044
  • Mohamed, H. M., El-Wahab, A. H. F. A., Ahmed, K. A., El-Agrody, A. M., Bedair, A. H., Eid, F. A., Khafagy, M. M. (2012). Synthesis, Reactions and Antimicrobial Activities of 8-Ethoxycoumarin Derivatives. Molecules, 17 (1), 971–988. doi: http://doi.org/10.3390/molecules17010971
  • Zhuravel, I., Kovalenko, S., Vlasov, S., Chernykh, V. (2005). Solution-phase Synthesis of a Combinatorial Library of 3-[4-(Coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid Amides. Molecules, 10 (2), 444–456. doi: http://doi.org/10.3390/10020444
  • KhanYusufzai, S., Osman, H., Khan, M. S., Mohamad, S., Sulaiman, O., Parumasivam, T. et. al. (2017). Design, characterization, in vitro antibacterial, antitubercular evaluation and structure–activity relationships of new hydrazinyl thiazolyl coumarin derivatives. Medicinal Chemistry Research, 26 (6), 1139–1148. doi: http://doi.org/10.1007/s00044-017-1820-2
  • Hamdi, M., Talhi, O., Silva, A., Lechani, N., Kheddis-Boutemeur, B., Laichi, Y., Bachari, K. (2018). Synthetic Approach Toward Heterocyclic Hybrids of [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazines. Synlett, 29 (11), 1502–1504. doi: http://doi.org/10.1055/s-0036-1591991
  • Bag, S., Ghosh, S., Tulsan, R., Sood, A., Zhou, W., Schifone, C. et. al. (2013). Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease. Bioorganic & Medicinal Chemistry Letters, 23 (9), 2614–2618. doi: http://doi.org/10.1016/j.bmcl.2013.02.103
  • Banerjee, A., Santra, S. K., Mishra, A., Khatun, N., Patel, B. K. (2015). Copper(i)-promoted cycloalkylation–peroxidation of unactivated alkenes via sp3C–H functionalisation. Organic & Biomolecular Chemistry, 13 (5), 1307–1312. doi: http://doi.org/10.1039/c4ob01962h
  • Widman, O. (1918). Über eine neue Gruppe von Cyclopropan-Derivaten. I: Die Einwirkung von Phenyl-acylhalogeniden auf 3-Acidyl-cumarine bei Gegenwart von Natriumalkoholat. Berichte Der Deutschen Chemischen Gesellschaft, 51 (1), 533–541. doi: http://doi.org/10.1002/cber.19180510165
  • Coyle, M. B. (2005). Manual of antimicrobial susceptibility testing. Washington, 29–39.
  • Bacteriological Control of Growth Media (2001). Information Letter of the Ukraine Ministry of Health No. 05.4.1/1670. Kyiv.
  • McFarland, J. (1907). The nephelometer: an instrument for estimating the number of bacteria in suspensions used for calculating the opsonic index and for vaccines. JAMA: The Journal of the American Medical Association, 49 (14), 1176–1178. doi: http://doi.org/10.1001/jama.1907.25320140022001f
  • Trott, O., Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31 (2), 455–461. doi: http://doi.org/10.1002/jcc.21334
  • Zhong, W., Pasunooti, K. K., Balamkundu, S., Wong, Y. W., Nah, Q., Liu, C. F. et. al. (2019). Crystal structure of TrmD from Pseudomonas aeruginosa in complex with active-site inhibitor. doi: http://doi.org/10.2210/pdb5zhm/pdb
  • Lazareva, A. V., Tchebotar, I. V., Kryzhanovskaya, O. A., Tchebotar, V. I., Mayanskiy, N. A. (2015). Pseudomonas aeruginosa: Pathogenicity, Pathogenesis and Diseases. Clinical Microbiology and Antimicrobial Chemotherapy, 17 (3), 170–186.
  • Zhong, W., Pasunooti, K. K., Balamkundu, S., Wong, Y. H., Nah, Q., Gadi, V. et. al. (2019). Thienopyrimidinone Derivatives That Inhibit Bacterial tRNA (Guanine37-N1)-Methyltransferase (TrmD) by Restructuring the Active Site with a Tyrosine-Flipping Mechanism. Journal of Medicinal Chemistry, 62 (17), 7788–7805. doi: http://doi.org/10.1021/acs.jmedchem.9b00582