Synthesis and pharmacological activities of some new 2-[1-Heptyl-3-(4-methoxybenzyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl] acetohydrazide derivatives

WOS: 000347145200004In the present investigation, the key intermediate acetohydrazide derivative 5 was synthesized starting from 3-(4-methoxybenzyl)-4-amino-4,5-dihydro-1,2,4-triazol-5-one (1) by a four-step reaction. Thiosemicarbazides 6a-f and arylidenehydrazide derivatives 8a-d were obtained from compound 5. the cyclization of compounds 6a-f in the presence of NaOH resulted in the formation of compounds 7a-f. the compounds were characterized by IR, H-1 NMR, C-13 NMR spectroscopy, elemental analysis and mass spectial studies. the compounds were tested for their anti-lipase, anti-alpha-glucosidase and anti-mycobacterial activities. Compounds 6b and 8c exhibited excellent anti-lipase activity, and compound 8d showed excellent anti-alpha-glucosidase activity. Compounds 3 and 4 exhibited good anti-tuberculosis activity.Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020]The support provided by Karadeniz Technical University, BAP, Turkey (project no. 10020) is gratefully acknowledged

Synthesis and evaluation of lipase inhibitory activities of substituted 1,2,4-triazole derivatives

1409-1417Pancreatic lipase (PL) plays a major role in the hydrolysis of dietary triglycerides to monoglycerides and free fatty acids in the small intestine before absorption of fats. The excessive consumption of dietary fat (triglyceride) and not to utilize it for energy production can cause an increase in obesity. Obesity is one of the serious health problem in the world and leads to many diseases such as some types of cancer, heart disease, gallstones, sleep apnea, fatty liver disease, type-2 diabetes, hypertension, coronary artery disease. Therefore, lipase is the target enzyme to prevent these diseases and the inhibitors of lipase are very important molecules as drug candidate molecules. In this study, fifteen new heterocyclic compounds have been synthesized starting from 2-[3-(4-chlorobenzyl)-5-(4-chlorophenyl)-1H-1,2,4-triazol-4-yl]-acetohydrazide and their anti-lipase activities have been examined. According to in vitro inhibition studies, molecule 2e is found to be the most potent inhibitor with the lowest IC50 value. Docking studies' results have substantially supported this result and it is seen that compound 2e is one of the four molecules with the highest binding affinity. This molecule binds to the enzyme in its binding pocket by means of weak interactions with mainly Ile79, Asp80, Val260, Arg257 and His264

Synthesis and evaluation of lipase inhibitory activities of substituted 1,2,4-triazole derivatives

Pancreatic lipase (PL) plays a major role in the hydrolysis of dietary triglycerides to monoglycerides and free fatty acids in the small intestine before absorption of fats. The excessive consumption of dietary fat (triglyceride) and not to utilize it for energy production can cause an increase in obesity. Obesity is one of the serious health problem in the world and leads to many diseases such as some types of cancer, heart disease, gallstones, sleep apnea, fatty liver disease, type-2 diabetes, hypertension, coronary artery disease. Therefore, lipase is the target enzyme to prevent these diseases and the inhibitors of lipase are very important molecules as drug candidate molecules. In this study, fifteen new heterocyclic compounds have been synthesized starting from 2-[3-(4-chlorobenzyl)-5-(4-chlorophenyl)-1H-1,2,4-triazol-4-yl]-acetohydrazide and their anti-lipase activities have been examined. According to in vitro inhibition studies, molecule 2e is found to be the most potent inhibitor with the lowest IC50 value. Docking studies' results have substantially supported this result and it is seen that compound 2e is one of the four molecules with the highest binding affinity. This molecule binds to the enzyme in its binding pocket by means of weak interactions with mainly Ile79, Asp80, Val260, Arg257 and His264.

Synthesis of New Bis-1,2,4-Triazole Derivatives

A series of new 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 4 were prepared in good yields bytreatment of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 2 with certain bis-aldehydes 1.Compounds 4 were reduced with NaBH4 to afford the corresponding 1,2/1,3-bis[o-(N-methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives5. All new compounds were characterized by IR, 1H-NMR, 13C-NMR and mass spectraldata

Synthesis of some 3,5-diphenyl-4<i>H</i>-1,2,4-triazole derivatives as antitumor agents

2107-2113 A series of 4-arylidenamino-4H-1,2,4-triazoles 2-14 and 4-(1-aryl)ethylidenamino-4H-1,2,4-triazoles 28-30 have been synthesized by the treatment of 4-amino-4H-1,2,4-triazole 1 with certain aldehydes and ketones. Compounds 2-14 and 28-30 have been reduced with NaBH4 to afford the corresponding 4-arylmethylamino-4H-1,2,4-triazoles 15-27 and 4-(1-aryl)ethylamino-4H-1,2,4-triazoles 31-33. The compounds 2-33 have been characterized by 1H NMR, 13C NMR, IR, Mass and UV-Vis spectral data. Compounds 12, 17, 18, 19, 20, 21, 22, 24, 29 and 32 have been screened on three human tumor cell lines, breast cancer (MCF7), non small cell lung cancer (NCI-H460), and CNS cancer (SF-268) at the National Cancer Institute (NIH), USA. The compounds are found to exhibit low antiproliferative activity in the anticancer tests. </smarttagtype

Synthesis of schiff and mannich bases of isatin derivatives with 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones

WOS: 000259735800007PubMed: 18830145Ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through solutions of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones 2 were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment of 2 with hydrazine hydrate leads to the formation of substituted 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones 3. Isatin and 5-chloroisatin were added to 3 to form Schiff bases 4 and N-Mannich bases 5 of these compounds were synthesized by reacting with formaldehyde and piperidine. Their chemical structures were confirmed by means of IR, H-1- and C-13-NMR data and by elemental analysis.Karadeniz Technical University Research Fund [2004.122.002.01]This work was supported by Karadeniz Technical University Research Fund (Project No: 2004.122.002.01)

Synthesis and kinetics studies of N '-(2-(3,5-disubstituted-4H-1,2,4-triazol-4-yl)acetyl)-6/7/8-substituted-2-oxo-2H-chromen-3-carbohydrazide derivatives as potent antidiabetic agents

WOS: 000490073000001PubMed: 31609028A novel series of N '-(2-(3,5-disubstituted-4H-1,2,4-triazol-4-yl)acetyl)-6/7/8-substituted-2-oxo-2H-chromen-3-carbohydrazides were synthesized and studied for their alpha-glucosidase inhibition activity. Most of the synthesized compounds exhibited potential alpha-glucosidase inhibition activity with IC50 values ranging from 0.96 +/- 0.02 to 32.86 +/- 0.73 mu g/ml. Among them, compounds 3e and 4e, having a methoxy group on the coumarin ring, proved to be the most potent ones, showing an enzyme inhibition activity with IC50 = 0.96 +/- 0.02 and 1.44 +/- 0.06 mu g/ml, respectively. the kinetic study through Lineweaver-Burk plots revealed that the inhibition mechanism of the most active compounds 3d, 3e, 4d, and 4e, on the alpha-glucosidase activity, was found to be in the competitive mode

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

WOS: 000369915500019PubMed: 25640970In 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.Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020]The support provided by Karadeniz Technical University, BAP, Turkey (Project No. 10020) is gratefully acknowledged

Synthesis and antimicrobial activity of some 3-alkyl-4-(arylmethyleneamino)-4,5-dihydro-1<i style="">H</i>-1,2,4-triazol-5-ones

2614-2617Eight new ethyl Nı-(3-methyl-4-arylmethyleneamino-4,5-di­hydro-1H-1,2,4-triazolyl-5-one)acetates 2 and Nı-(3-methyl-4-arylmethyleneamino-4,5-dihydro-1H-1,2,4-triazolyl-5-one)acetyl­hydrazines 3 have been synthesized. The structures of the compounds have been confirmed by IR and 1H NMR spectra and microanalysis. The compounds show some antimicrobial activities. Compound 2a shows antibacterial activity against B. subtilis. Compounds 3a, 3b and 3d have antifungal activity against Candida species

Synthesis of some N-alkoxycarbonyl-N ''-benzoyl-benzamidrazones(p-toluamidrazones) and 1,3,5-trisubstituted 1,2,4-triazole derivatives from N-benzoylimidates and their antimicrobial and anticancer screening studies

WOS: 000251996400018Some new N-alkoxycarbonyl-N ''-benzoyl-benzamidrazones (p-toluamidrazones) 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, H-1 NMR, C-13 NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer (MCF7), non small cell lung cancer (NCI-H460), and CNS cancer (SF-268) at the National Cancer Institute (NCI), USA, which were found to exhibit low antiproliferative activity