title: 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 α-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, (1)H NMR, (13)C NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and α-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 ± 0.50 µM) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 ± 0.16 µM) and 6a (IC50 = 4.36 ± 0.10 µM) showed the best anti-α-glucosidase activity.
authors: a Department of Chemistry, Faculty of Science , Karadeniz Technical University , Trabzon , Turkey .
authors: Olcay
authors: O
authors: Bekircan
authors: b Department of Biology , and.
authors: Serdar
authors: S
authors: Ülker
authors: c Department of Chemistry , Faculty of Arts and Sciences, Recep Tayyip Erdogan University , Rize , Turkey.
authors: Emre
authors: E
authors: Menteşe
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: C000608075:2-((3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl)acetyl)-4-(4-chlorophenyl)thiosemicarbazide; C000608076:5-(((3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl))methyl))-3-((4-methylpiperazin-1-yl)methyl)-1,3,4-oxadiazole-2(3H)-thione; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D010069:Oxadiazoles; D012663:Semicarbazides; D014230:Triazoles; D008049:Lipase; D000520:alpha-Glucosidases
keywords: 1,2,4-triazole-5-thiones; 1,2,4-triazoles; 1,3,4-oxadiazoles; Biheterocyclic compounds; Mannich bases; lipase and α-glucosidase inhibition