Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis, Urease and Acetylcholine Esterase Inhibition Activities of Some 1,4-Disubstituted Thiosemicarbazides and their 2,5-Disubstituted Thiadiazoles

  • Received : 2012.04.04
  • Accepted : 2012.05.29
  • Published : 2012.08.20
Download PDF
⟨ Previous Next ⟩

Abstract

A new series of 2,5-disubstituted-1,3,4-thiadiazoles 6a-i was synthesized by overnight stirring various 1,4-disubstituted thiosemicarbazides 5a-i in polyphosphoric acid followed by neutralization. The structures of newly synthesized compounds 5a-i and 6a-i were characterized by IR, $^1H$ and $^{13}C$ NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were evaluated for their urease and acetylcholine esterase inhibition activities. Thiosemicarbazides 5a-i are found to possess excellent potential for urease inhibition, more than the standard drug. Thiosemicarbazides 5a-i are more potent urease inhibitor than their cyclic analogues thiadiazoles 6a-i. Almost all of the compounds are excellent inhibitors of acetylcholine esterase. The inhibition of acetylcholine esterase of compounds 5a, 5c, 5d, 5g, 5i, 6e, 6f, 6g, and 6i is much more than that of standard drug.

Keywords

References

  1. Li, M.; Ding, W.; Baruah, B.; Crans, D. C.; Wang, R. J. Inorg. Biochem. 2008, 102, 1846-1853. https://doi.org/10.1016/j.jinorgbio.2008.06.007
  2. Mobley, H. L.; Hausinger, R. P. Microbiol. Rev. 1989, 53, 85-108.
  3. Karplus, P. A.; Pearson, M. A.; Hausinger, R. P. Acc. Chem. Res. 1997, 30, 330-337. https://doi.org/10.1021/ar960022j
  4. Collins, C. M.; D-Orazio, S. E. F. Mol. Microbiol. 1993, 9, 907- 913. https://doi.org/10.1111/j.1365-2958.1993.tb01220.x
  5. Montecucco, C.; Rappuoli, R. Nat. Rev. Mol. Cell Biol. 2001, 2, 457-466. https://doi.org/10.1038/35073084
  6. Hausinger, R. P.; Karplus, P. A. In Handbook of Metalloproteins; Messerschmidt, A., Hubber, R., Poulos, T., Wieghardt, K., Eds.; Wiley: Chichester, 2001.
  7. Zhengping, W.; Cleemput, O. V.; Demeyer, P.; Baert, L. Biol. Fertil. Soils 1991, 11, 41-47.
  8. Changeux, J. P. Mol. Pharmacol. 1966, 2, 369-392.
  9. Epstein, D. J.; Berman, H. A.; Taylor, P. Biochem. 1979, 18, 4749- 4754. https://doi.org/10.1021/bi00588a040
  10. Mallender, W. D.; Szeglets, T.; Rosenberry, T. L. J. Biol. Chem. 1999, 274, 8491-8499. https://doi.org/10.1074/jbc.274.13.8491
  11. Szeglets, T.; Mallender, W. D.; Thomas, P. J.; Rosenberry, T. L. Biochem. 1999, 38, 122-133. https://doi.org/10.1021/bi9813577
  12. Abramov, A. Y.; Canvari, L.; Duchen, M. R. J. Neurosci. 2003, 15, 5088-5095.
  13. Butterfield, D. A. Chem. Res. Toxicol. 1997, 10, 495-506. https://doi.org/10.1021/tx960130e
  14. Marchbanks, R. M. J. Neurochem. 1982, 39, 9-15. https://doi.org/10.1111/j.1471-4159.1982.tb04695.x
  15. Taylor, P. Pharmacological Basis of Therapeutics; Gilman, A. G., Goodman, L. S., Murad, F., Eds.; MacMillan: New York, 1985.
  16. Ellis, J. M. J. Am. Osteopth Assoc. 2005, 105, 145-158.
  17. Farlow, M.; Gracon, S. I.; Hershey, L. A.; Lewis, K. W.; Sadowsky, C. H. J. Dolan-Ureno, Jama. 1992, 268, 2523-2529. https://doi.org/10.1001/jama.1992.03490180055026
  18. Lahiri, D. K.; Farlow, M. R.; Grieg, N. H.; Sambamurti, K. Drug Dev. Res. 2002, 56, 267-281. https://doi.org/10.1002/ddr.10081
  19. Rogers, S. L.; Farlow, M. R.; Doody, R. S.; Mohs, R.; Friedhoff, L. T. Neurology 1998, 50, 136-145. https://doi.org/10.1212/WNL.50.1.136
  20. Ellman, G. L.; Courtney, K. D.; Andres, V., Jr.; Feather-Stone, R. M. Biochem. Pharmacol. 1961, 7, 88-95 https://doi.org/10.1016/0006-2952(61)90145-9
  21. Song, C.; Xuhong, Q.; Gonghua, S.; Qingchun, H. J. Flour. Chem. 2002, 117, 63-66. https://doi.org/10.1016/S0022-1139(02)00172-0
  22. Hebert, N.; Hannah, A. L.; Sutton, S. C. Tetrahedron Lett. 1999, 40, 8547-8550. https://doi.org/10.1016/S0040-4039(99)01826-2
  23. Rehman, A.; Choudhry, M. I.; Thomsen, W. J. Bioassay Technique for Drug Development; Harwood Academic Publishers: The Netherland, 2001; p 22.
  24. Khan, I.; Ali, S.; Hameed, S.; Rama, N. H.; Hussain, M. T.; Wadood, A.; Uddin, R.; UL-Haq, Z.; Khan, A.; Ali, S.; Choudhary, M. I. Eur. J. Med. Chem. 2010, 45, 5200-5207. https://doi.org/10.1016/j.ejmech.2010.08.034
  25. Weatherburn, M. W. Anal Chem. 1967, 39, 971.