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RESEARCH ARTICLE
Contents Vol 65(10)

Synthesis, Acetylcholinesterase and Alkaline Phosphatase Inhibition of Some New 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives

Imtiaz Khan A , Muhammad Hanif A , Muhammad Tahir Hussain B , Aftab Ahmed Khan C , Muhammad Adil S. Aslam C , Nasim Hasan Rama A D and Jamshed Iqbal C D
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.

B Department of Applied Sciences, National Textile University, Faisalabad 37610, Pakistan.

C Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.

D Corresponding authors. Email: nhrama@qau.edu.pk; drjamshed@ciit.net.pk

Australian Journal of Chemistry 65(10) 1413-1419 https://doi.org/10.1071/CH12134
Submitted: 4 March 2012  Accepted: 18 May 2012   Published: 27 August 2012

Abstract

A new series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (6a–s) and 2,5-disubstituted-1,3,4-thiadiazoles (7a–h) was synthesized by intramolecular dehydrocyclization of various 1,4-disubstituted thiosemicarbazide derivatives (5a–s) by refluxing in 4 N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of these compounds were characterized by IR, 1H and 13C NMR, elemental analysis and mass spectroscopic studies. All the synthesized compounds were screened for their acetylcholinesterase and alkaline phosphatase inhibition studies. Most of the tested compounds showed promising activities, amongst them (6k) and (6q) showed excellent acetylcholinesterase inhibitory activity with IC50 0.241 ± 0.012 and 0.260 ± 0.013 µM, respectively, as compared with those of standard drug whereas the compound (6p), with IC50 0.044 ± 0.001 µM, was found to be the most potent inhibitor of alkaline phosphatase.


References

[1]  J. P. Changeux, Mol. Pharmacol. 1966, 2, 369.
         | 1:STN:280:DyaF2s7nvV2jtQ%3D%3D&md5=11aae4d43181a37e57fcc71e77e4eef2CAS |

[2]  D. J. Epstein, H. A. Berman, P. Taylor, Biochemistry 1979, 18, 4749.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1MXlslSktrg%3D&md5=2b8b0a56fb8d1a8dbf88665ed25442b3CAS |

[3]  W. D. Mallender, T. Szeglets, T. L. Rosenberry, J. Biol. Chem. 1999, 274, 8491.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXitFyrs7Y%3D&md5=c6e7c3082ff77c651ceb2160a58d50fbCAS |

[4]  T. Szegletes, W. D. Mallender, P. J. Thomas, T. L. Rosenberry, Biochemistry 1999, 38, 122.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnvVKlsL8%3D&md5=a3d79d62e6b72e8d0874d5d9aa846b09CAS |

[5]  A. Y. Abramov, L. Canvari, M. R. Duchen, J. Neurosci. 2003, 15, 5088.

[6]  D. A. Butterfield, Chem. Res. Toxicol. 1997, 10, 495.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXjtlGjtr8%3D&md5=52fce07d4d16e025e44fc5d89ec7f535CAS |

[7]  R. M. Marchbanks, J. Neurochem. 1982, 39, 9.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XltVOqtb8%3D&md5=8e163de0502d6f1eb502ce5423642553CAS |

[8]  P. Taylor, Pharmacological basis of therapeutics, 1985 (Eds A. G. Gilman, L. S. Goodman, F. Murad) (MacMillan: New York).

[9]  J. M. Ellis, J. Am. Osteopath. Assoc. 2005, 105, 145.

[10]  B. N. Lenta, C. Vonthron-Sénécheau, B. Weniger, K. P. Devkota, J. Ngoupayo, M. Kaiser, Q. Naz, M. I. Choudhary, E. Tsamo, N. Sewald, Molecules 2007, 12, 1548.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFGntL3I&md5=2e2cc04307799e62f2359e455c208197CAS |

[11]  M. Farlow, S. I. Gracon, L. A. Hershey, K. W. Lewis, C. H. Sadowsky, J. Dolan-Ureno, JAMA 1992, 268, 2523.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s%2FitFKntg%3D%3D&md5=dd2c7bb6aed39bd6a116c189ae5fe90aCAS |

[12]  D. K. Lahiri, M. R. Farlow, N. H. Grieg, K. Sambamurti, Drug Dev. Res. 2002, 56, 267.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnvFGgtL0%3D&md5=9cc674fd63cf3d5e4ddacb47e9b306a3CAS |

[13]  S. L. Rogers, M. R. Farlow, R. S. Doody, R. Mohs, L. T. Friedhoff, Neurology 1998, 50, 136.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXotVKjsA%3D%3D&md5=0cb9102cd598e183af87b224aecff50dCAS |

[14]  M. H. Le Du, J. L. Millan, J. Biol. Chem. 2002, 277, 49808.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XpsFaktLo%3D&md5=71791483142df213132b0fdd0713167eCAS |

[15]  L. Zhang, M. Balcerzak, J. Radisson, C. Thouverey, S. Pikula, G. Azzar, R. Buchet, J. Biol. Chem. 2005, 280, 37289.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFKhtLjL&md5=5e9bf349a8564f0420caef6024ab071cCAS |

[16]  S. P. Coburn, J. D. Mahuren, M. Jain, Y. Zubovic, J. Wortsman, J. Clin. Endocrinol. Metab. 1998, 83, 3951.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXntlOit7o%3D&md5=0024d2eea862470d124eb3bcae04895dCAS |

[17]  D. Sarrouilhe, P. Lalegerie, M. Baudry, Biochim. Biophys. Acta 1992, 1118, 116.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XlsVeruw%3D%3D&md5=65fdd765818066f42449e1c5b415b3ceCAS |

[18]  M. Muda, N. N. Rao, A. Torriani, J. Bacteriol. 1992, 174, 8057.
         | 1:CAS:528:DyaK3sXns1yitw%3D%3D&md5=8410e1e687e08c643f100fbec7f88c0bCAS |

[19]  M. Li, W. Ding, B. Baruah, D. C. Crans, R. Wang, J. Inorg. Biochem. 2008, 102, 1846.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVyktr3N&md5=8c954d9f123478bdea780c3ab913465dCAS |

[20]  A. Katrizky, Comprehensive Heterocyclic Chemistry, 1984, vol. 6, (Pergamon: Oxford, London).

[21]  M. S. Karthikeyan, B. S. Holla, Monatsh. Chem. 2008, 139, 691.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmsVens7s%3D&md5=ff1baf7d8e4adfffe88974ce27e56824CAS |

[22]  I. Khan, S. Ali, S. Hameed, N. H. Rama, M. T. Hussain, A. Wadood, R. Uddin, Z. U. Haq, A. Khan, S. Ali, M. I. Choudhary, Eur. J. Med. Chem. 2010, 45, 5200.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1KrtrbP&md5=f0f955d041701b62768890aa662e55b0CAS |

[23]  O. R. Abid, T. M. Babar, F. I. Ali, S. Ahmed, A. Wadood, N. H. Rama, Z. U. Haq, R. Uddin, A. Khan, M. I. Choudhary, ACS Med. Chem. Lett 2010, 51, 145.

[24]  X. Zheng, Z. Li, Y. Wang, W. Chen, Q. Huang, C. Liu, G. Song, J. Fluor. Chem. 2003, 123, 163.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnvFGgsLw%3D&md5=d0affe1d956bc58ebfee4a9901f3cdfbCAS |

[25]  M. Moise, V. Sunel, L. Profire, M. Popa, J. Desbrieres, C. Peptu, Molecules 2009, 14, 2621.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  W. Shi, X. Qian, R. Zhang, G. Song, J. Agric. Food Chem. 2001, 49, 124.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXovFOjtbg%3D&md5=28f775b3b92e3c681e163a66b75bfb5eCAS |

[27]  M. Amir, K. Shikha, Eur. J. Med. Chem. 2004, 39, 535.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXks1Grt7w%3D&md5=d774b738e2e61272b40e97644a079495CAS |

[28]  H. Gilman, A. H. Blatt, Organic Synthesis Coll., 1967, 2nd ed. (John Wiley Inc: New York).

[29]  G. L. Ellman, K. D. Courtney, V. Andres, R. M. Feather-Stone, Biochem. Pharmacol. 1961, 7, 88.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3MXht1Gns7o%3D&md5=498216e0675cc10622232761e6994538CAS |

[30]  J. Iqbal, Anal. Biochem. 2011, 414, 226.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmsVWksbY%3D&md5=a188adc5f87edce552d2e9c2db3a3805CAS |

[31]  M. Hanif, G. Qadeer, N. H. Rama, S. Vuoti, J. Autio, Acta Crystallogr. 2007, E63, o4754.
         | 1:CAS:528:DC%2BD2sXhtlKlsbjE&md5=57d6f464a2821aa67ca3e93d70dfa0c6CAS |