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Medicinal Chemistry Research

, Volume 27, Issue 6, pp 1647–1665 | Cite as

Synthesis, X-ray crystallographic study, pharmacology and docking of hydrazinyl thiazolyl coumarins as dengue virus NS2B/NS3 serine protease inhibitors

  • Samina Khan Yusufzai
  • Hasnah Osman
  • Mohammad Shaheen Khan
  • Basma M. Abd Razik
  • Suriyati Mohamad
  • Othman Sulaiman
  • Jualang Azlan Gansau
  • Norhaniza Johansah
  • Mohammed Oday Ezzat
  • Thaigarajan Parumasivam
  • Mohd Mustaqim Rosli
  • Ibrahim Abdul Razak
Original Research

Abstract

A series of total twenty-one thiazole-coumarin derivatives 7a-u, linked via hydrazine linkage were synthesized through Hantzsch cyclisation. Out of twenty-one derivatives, fourteen derivatives viz. 7b-d, 7g, 7i-k, 7n and 7p-u are the novel derivatives. The structures of the synthesized compounds were established by extensive spectroscopic studies (FTIR, 1H NMR, 13C NMR, 2D NMR, LC-MS) and elemental analysis. The structure of (E)-6-methoxy-3-(1-(2-(4-p-tolylthiazol-2-yl)hydrazono)ethyl)-2H-chromen-2-one (7d) was unambiguously confirmed by X-ray crystallography analysis. Hybrid molecules were evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Eschericia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus. All the compounds displayed considerable potency against all the pathogens with MIC values ranging from 31.25 to 250 μg/mL, therein compounds 7i, 7j, 7k, 7q and 7t displayed superior inhibitory activities compared to standard drugs streptomycin, kanamycin, vancomycin and isoniazid. Molecular docking studies were performed to check the potential as dengue virus NS2B/NS3 serine protease inhibitors, by comparing to standards 4-hydroxypanduratin, panduratin and ethyl 3-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy)propanoate with DS of −3.379, −3.189 and −3.381, respectively. All the compounds were found to exhibit potency against the DENV virus. In particular, compound 7c (DS –5.141) and 7l (DS –3.894) were found to be even better than the standards followed by compounds 7j (DS –3.113) and 7q (DS –3.561).

Keywords

Molecular docking Docking score Anti-bacterial activity Anti-tuberculosis activity Anti-dengue activity 

Notes

Acknowledgements

We would like to thank the Malaysian Government and Universiti Sains Malaysia (USM) for providing necessary research facilities and Research University Grant (FRGS 203/PKIMIA/6711462). Samina Khan Yusufzai (SKY) thanks the Institute of Postgraduate Studies (IPS), USM for the Graduate Assistance fellowship support. SKY expresses the gratitude to the School of Biological Sciences, USM and Faculty of Science and Natural Resources, Universiti Malaysia Sabah for providing facilities for biological studies.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2179_MOESM1_ESM.doc (1.9 mb)
Supplementary Material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Samina Khan Yusufzai
    • 1
    • 2
  • Hasnah Osman
    • 1
  • Mohammad Shaheen Khan
    • 3
  • Basma M. Abd Razik
    • 4
  • Suriyati Mohamad
    • 5
  • Othman Sulaiman
    • 2
  • Jualang Azlan Gansau
    • 6
  • Norhaniza Johansah
    • 6
  • Mohammed Oday Ezzat
    • 7
  • Thaigarajan Parumasivam
    • 8
  • Mohd Mustaqim Rosli
    • 9
  • Ibrahim Abdul Razak
    • 9
  1. 1.School of Chemical SciencesUniversiti Sains MalaysiaPenangMalaysia
  2. 2.School of Industrial TechnologyUniversiti Sains MalaysiaPenangMalaysia
  3. 3.Industrial Chemistry Programme, Faculty of Science and Natural ResourcesUniversiti Malaysia SabahSabahMalaysia
  4. 4.College of PharmacyAl-Mustansiriyah UniversityBaghdadIraq
  5. 5.School of Biological SciencesUniversiti Sains MalaysiaPenangMalaysia
  6. 6.Biotechnology Programme, Faculty of Science and Natural ResourcesUniversiti Malaysia SabahKota KinabaluMalaysia
  7. 7.College of Education for WomenUniversity of AnbarRamadiIraq
  8. 8.School of Pharmaceutical SciencesUniversiti Sains MalaysiaPenangMalaysia
  9. 9.X-Ray Crystallography Unit, School of PhysicsUniversiti Sains MalaysiaPenangMalaysia

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