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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
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 http://dx.doi.org/10.1071/CH12134
Submitted: 4 March 2012 Accepted: 18 May 2012 Published:
27
August
2012
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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. 
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