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Synthesis and Evaluation of 1,-Bis(1,2,3,5-thiatriazol-5-yl)alkanes as In Vitro and In Vivo -Amylase and Lipase Inhibitors

Abstract : Thionyl chloride reacts with 1,-bis-(1-tosylamidrazone)alkanes 1 to give a series of 1,-bis-(4-alkyl-2-tosyl-1,2,3,5-thiatriazol-5-yl)alkanes 2. All the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis, and ESIMS spectral data. All the new compounds were screened for their inhibitory effect on key enzymes related to diabetes and obesity, such as -amylase and lipase. In vitro and in vivo studies revealed that these thiatriazole derivatives exert an inhibitory action against these key enzymes. Moreover the administration of these compounds to surviving diabetic rats induced a significant decrease in plasma glucose level. Additively 2d significantly protected the liverkidney functions and modulated lipid metabolism, which were evidenced by the decrease in aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) activities and creatinine, urea albumin, LDL-cholesterol and triglycerides levels as well as an increase in the HDL-cholesterol level in surviving diabetic rats. Overall, the findings of the current study indicate that 2d exhibits attractive properties and can, therefore, be considered for future application in the development of anti-diabetic and hypolipidemic drugs.
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Submitted on : Wednesday, March 22, 2017 - 4:40:29 PM
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Salwa Hamzaoui, Khaled Hamden, Adel Ben Salem, Maxime Mourer, Jean-Bernard Regnouf-De-Vains, et al.. Synthesis and Evaluation of 1,-Bis(1,2,3,5-thiatriazol-5-yl)alkanes as In Vitro and In Vivo -Amylase and Lipase Inhibitors. Archiv der Pharmazie / Chemistry in Life Sciences, Wiley-VCH Verlag, 2013, 346 (4), pp.321-329. ⟨10.1002/ardp.201200312⟩. ⟨hal-01494089⟩

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