Synthesis of some novel heterocylic compounds derived from 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide and investigation of their lipase and alpha-glucosidase inhibition

Abstract

In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-1,3,4-oxadiazole-2-thione (5). the cyclization of compounds 2a-c in the presence of NaOH resulted in the formation of 5-{[3-( 4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones(3a-c). Aminomethylation of compounds 3a-c and 5 with formaldehyde and N-methyl/phenylpiperazine furnished Mannich bases (4a-f and 6a-b). the newly synthesized compounds were well-characterized by IR, H-1 NMR, C-13 NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and alpha-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 +/- 0.50 mu M) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 +/- 0.16 mu M) and 6a (IC50 = 4.36 +/- 0.10 mu M) showed the best anti-alpha- glucosidase activity.