Emre Menteşe

Microwave-assisted synthesis of new benzimidazole derivatives with lipase inhibition activity

Abstract A practical protocol has been used for the synthesis of benzimidazoles. The reaction of iminoester hydrochlorides of phenylacetic with 4,5-dichloro-1,2-phenylenediamine under microwave irradiation leads to the benzimidazole derivatives with good yields and in short reaction times. After the synthesis of benzimidazoles, we synthesized ester and hydrazide derivatives under microwave irradiation with good yields. All compounds were evaluated with regard to pancreatic lipase activity and 3b, 3c, 5a and 6a showed lipase inhibition at various concentrations.

Microwave-Assisted Synthesis and Biological Evaluation of Some Benzimidazole Derivatives Containing a 1,2,4-Triazol Ring

A new series of 2‐(4‐(trifluoromethyl)phenyl)‐1H‐benzo[d]imidazole derivatives containing a 1,2,4‐triazole ring were synthesized via microwave technique. This efficient procedure provides pure products within a few minutes. The newly synthesized compounds were confirmed by 1H NMR and 13C NMR spectra and they were screened for their lipase inhibition and antioxidant activities. Compounds 4a, 4b, 5a, and 5b showed very good scavenging activity.

Synthesis of Some New 1,2,4‐Triazole Derivatives Starting from 3‐(4‐Chlorophenyl)‐5‐(4‐methoxybenzyl)‐4H‐1,2,4‐triazol with Anti‐Lipase and Anti‐Urease Activities

In the present study, starting compound 4 was prepared by deamination of compound 2 in the presence of hypophosphorous acid and sodium nitrite. Treatment of compound 4 with ethyl bromoacetate produced ethyl[3‐(4‐chlorophenyl)‐5‐(4‐methoxybenzyl)‐4H‐1,2,4‐triazol‐4‐yl]acetate (5), which was converted to the hydrazide derivative (6) by treatment with hydrazine hydrate. The reaction of compound 6 with aromatic aldehydes resulted in the formation of arylidene hydrazides (7). Treatment of 6 with CS2 in the presence of potassium hydroxide (KOH), followed by cyclization with hydrazine hydrate, afforded 4‐amino‐5‐{[3‐(4‐chlorophenyl)‐5‐(4‐methoxybenzyl)‐4H‐1,2,4‐triazol‐4‐yl]methyl}‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thione (9). The condensation of 9 with appropriate aldehydes gave Schiff bases (10), which were converted into Mannich bases (11) in the presence of formaldehyde. All the synthesized compounds were screened for their anti‐lipase and anti‐urease activities. Compounds 7b, 7d, 11b, 11c, and 11d showed moderate‐to‐good lipase inhibitory effects compared to orlistat. Compounds 7b and 7d exhibited better anti‐lipase activity. Furthermore, among the compounds tested, 11a and 11d were found to show high inhibitory effect against urease with IC50 values of 12.39 ± 0.35 and 16.12 ± 1.06 µg/mL, respectively. Compound 11c showed moderate inhibitory activity. The Mannich base containing compound 11 may be a source of good leads for the synthesis of lipase and urease dual inhibitors.

Synthesis of Some Novel 1,2,4‐Triazol‐3‐one Derivatives Bearing the Salicyl Moiety and Their Anticonvulsant Activities

A series of new 1,2,4‐triazole‐3‐one derivatives bearing the salicyl moiety were synthesized by using microwave irradiation, and their chemical structures were identified by IR, 1H NMR, 13C NMR, elemental analysis, and LC‐MS. The anticonvulsant activities of the compounds 4a–c, 4e, and 5a–e were evaluated by the Anticonvulsant Screening Program of the National Institute of Health, USA. The compounds had moderate anticonvulsant activities in the maximum electroshock‐induced seizure and minimal clonic seizure models in mice, without any neurotoxic effects.

Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings

Abstract Various triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings (3–6) were synthesized and screened for their antioxidant activities. The structures of the synthesized compounds (2–6) were judged by 1H NMR, 13C NMR, elemental analysis, and LC-MS spectral data. Antioxidant activities of the synthesized compounds (2–6) were determined with CUPric Reducing Antioxidant Capacity (CUPRAC), ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)/persulfate, and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. Most of the compounds showed a significant antioxidant activity and especially, compound 5c showed very good SC50 value for DPPH method and compound 5h exhibited very high scavenging activity to ABTS method.

Effect of microwave irradiation on the synthesis of 1,2,4-triazol-3-one derivatives and their antimicrobial activities

An easy efficient method for the synthesis of N-(3,5-dichlorophenyl)-5-alkyl/aryl-3H-1,2,4-triazol-3-one derivatives under microwave irradiation has been developed using the reaction of 3,5-dichloroaniline and ethoxycarbonylhydrazones. This reaction occurs more efficiently and faster than the conventional heating method. We obtained 5-mercapto-1,3,4-oxadiazol derivatives by this method. The newly synthesised compounds have been tested for their antimicrobial activity against Enterobacter cloaceae, Escherichia coli, Klebsiella pneumonie, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimurium, Yersinia pseudotuberculosis, Bacillus subtilis and Staphylococcus aereus.

Synthesis and Study of α-Glucosidase Inhibitory, Antimicrobial and Antioxidant Activities of Some Benzimidazole Derivatives Containing Triazole, Thiadiazole, Oxadiazole, and Morpholine Rings

A new series of 2-(4-bromobenzyl)- and 2-(4-fluorobenzyl)-1H-benzimidazole derivatives containing 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole, and morpholine rings has been synthesized. The structures of the newly synthesized compounds were confirmed by 1H and 13C NMR and mass spectra, and all substances have been screened for their α-glucosidase inhibitory, antimicrobial and antioxidant activities. Hydrazide, oxadiazole, thiosemicarbazide, and 1,2,4-triazole-3-thiol derivatives showed very good ABTS scavenging activities (IC50 1.94-4.79 μM). Oxadiazole and thiosemicarbazide derivatives also revealed notable DPPH scavenging activity. 5-[(2-(4-Bromobenzyl)-1H-benzimidazol-1-yl)methyl]-1,3,4-oxadiazole-2-thiol was found to be more potent than acarbose. 2-(4-Fluorobenzyl)-1H-benz- imidazole was effective against both Gram-positive and Gram-negative bacteria, especially, M. smegmatis.

Synthesis and molecular docking study of some 5,6-dichloro-2-cyclopropyl-1H-benzimidazole derivatives bearing triazole, oxadiazole, and imine functionalities as potent inhibitors of urease

A new series of benzimidazole compounds including hydrazinecarbothioamide, 1,2,4-triazole, 1,3,4-oxadiazole and imine function were synthesized starting from 5,6-dichloro-2-cyclopropyl-1H-benzimidazole. All of the benzimidazole derivatives exhibited good urease inhibitor activity. Compound 6a proved to be the most potent showing an enzyme inhibitory activity with an IC50=0.06µM. Molecular docking studies were also conducted on enzyme extracted from Jack bean urease to identify the binding mode of the newly synthesized compounds.

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, 1H NMR, 13C 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.

Green Protocol: Solvent- and Catalyst-Free Synthesis of Benzimidazole Derivatives via Microwave Technique

A simple and green protocol has been developed for the synthesis of benzimidazoles. In this protocol, 2-[(alkyl/aryl)(ethoxy)methylidene]hydrazinecarboxylates with 1,2-phenylenediamine derivatives under solvent- and catalyst-free conditions under microwave irradiation lead to products with good yields in short reaction times.