Effects of increased physical activity and/or weight loss diet on serum myokine and adipokine levels in overweight adults with impaired glucose metabolism.

AIM: The purpose of this study was to investigate the changes in serum irisin, fibroblast growth factor-21 (FGF21), visfatin, follistatin like protein-1 (FSTL1), and meteorin-like protein (Metrnl) levels in response to increased physical activity and/or diet interventions in overweight subjects with impaired glucose metabolism (IGM). METHODS: A total of 60 subjects (BMI > 25.0 kg/m2) with IGM were recruited in this single-centered interventional study. Twelve subjects dropped out during the study and the study was completed with 48 patients. Patients were divided into two groups as diet only (DI, n = 24) and diet and physical activity intervention (DPA, n = 24). Patients in DI group received a diet program while DPA group received a diet combined with a physical activity intervention for 12 weeks. Additional 24 healthy subjects were recruited to compare the baseline levels of proteins. Serum protein levels, anthropometric measurements, and biochemical parameters were assessed. RESULTS: Irisin, FGF21, visfatin, and FSTL1 levels significantly decreased in both groups after 12-week intervention (p < 0.001). However, there were no differences in protein levels between DI and DPA groups (p > 0.05). Likewise, the total change in weight was similar in both DI (-4.35 kg) and DPA (-4.85 kg) groups (p > 0.05). A 5% reduction in initial body weight with DPA therapy resulted in a stronger correlation between the changes in irisin, visfatin, and FSTL1 levels and fasting glucose and HbA1c levels. CONCLUSIONS: These results demonstrate that serum irisin, FGF21, visfatin, and FSTL1 levels decreased in response to weight loss interventions. Weight loss induced by DI or DPA therapies had similar lowering effects on these proteins in subjects with IGM, and these myokines might be related to glucose metabolism biomarkers.

A 4-week diet with exercise intervention had a better effect on blood glucose levels compared to diet only intervention in obese individuals with insulin resistance.

BACKGROUND: The majority of prediabetic people are overweight and weight loss is still the most effective treatment strategy. The aim of this study was to evaluate the effects of short-term exercise and/or diet on weight loss and clinical parameters in subjects with insulin resistance (IR). METHODS: A total of 60 subjects (BMI≥25.0 kg/m2) were included in the study. Subjects divided into two groups as follows: diet only (DI, N.=27) and diet and exercise (DEI, N.=27). DI group received an energy restricted diet program, while DEI group received a diet combined with an exercise program for four weeks. Anthropometric measurements and biochemical parameters were assessed at baseline and at the end. RESULTS: Total body weight (BW) loss was 2.3 kg (2.5%) in DI group and 3.0 kg (3.2%) in DEI group at the end of four weeks. Fasting blood glucose (FBG) levels decreased significantly in DEI group (P=0.021). However, the reductions in FBG levels were mild and not statistically significant in DI group (P>0.05). Total cholesterol and LDL-c levels reduced in both groups, while triglyceride levels significantly decreased only in DI group (P<0.05). CONCLUSIONS: Short-term lifestyle interventions have beneficial effects on weight loss and clinical parameters associated with glucose control and lipid profile in subjects with IR. Even small changes in BW (loss of <5% of initial BW) have a positive impact on clinical parameters.

Synthesis and anticancer activities of some new coumarin derivatives including the triazole ring and their in silico molecular docking studies.

The synthesis, docking study, and investigation of the anticancer activities of some coumarin derivatives containing the triazole ring are reported in this study. The newly synthesized compounds were screened for their in vitro anticancer activity against the cell lines CRL5807 (human bronchioalveolar carcinoma), CRL5826 (human squamous cell carcinoma), MDA-MB231 (human breast cancer cells), HTB177 (human lung cancer), PC-3 (human prostate adenocarcinoma), PANC-1 (human pancreatic cancer cells), used as cancer cells, and CCD34Lu (normal human lung fibroblasts), used as a healthy cell line. Cytotoxicity effects of the samples were determined by the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. In silico studies were also performed to explore the binding interactions of the molecules.

Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors.

In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC50 values of 1.72 ±â€¯0.12 µM, 1.92 ±â€¯0.28 and 0.98 ±â€¯0.07 µM, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms.

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.

Design, Synthesis, and Biological Evaluation of Coumarin-Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents.

The design, synthesis, and investigation of antitumor and anti-lipase activities of some coumarin-triazole hybrid molecules are reported. The synthesis of these hybrid molecules was performed under microwave irradiation and conventional heating procedures. The newly synthesized hybrid molecules were investigated as inhibitors against four tumor cell lines (BT20 human breast carcinoma, SK-Mel 128 melanoma, DU-145 prostate carcinoma, and A549 lung carcinoma) and porcine pancreatic lipase (PPL). Most of these compounds showed notable antitumor activities against the tested tumor cell lines, and compounds 8i and 8l showed the best anti-lipase activity of 99.30 ± 0.56% and 99.85 ± 1.21%, respectively, at a concentration of 10 µM.

Synthesis of Some Novel 2-Substitutedbenzyl-(4)7-phenyl-1H-benzo[d]imidazoles in Mild Conditions as Potent Anti-Tyrosinase and Antioxidant Agents.

Novel 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 µM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 ± 0.24 µM) to the positive control, kojic acid (IC50 = 21.93 ± 0.11 µM). Kinetic studies revealed it to act as non-competitive tyrosinase inhibitor with a Ki value of 50.2 µM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors.

A simple and efficient synthesis of novel inhibitors of alpha-glucosidase based on benzimidazole skeleton and molecular docking studies.

A novel series of benzimidazole derivatives were prepared starting from o-phenylenediamine and 4-nitro-o-phenylenediamine with iminoester hydrochlorides. Acidic proton in benzimidazole was exchanged with ethyl bromoacetate, then ethyl ester group was transformed into hydrazide group. Cyclization using CS2/KOH leads to the corresponding 1,3,4-oxadiazole derivative, which was treated with phenyl isothiocyanate resulted in carbothioamide group, respectively. As the target compounds, triazole derivative was obtained under basic condition and thiadiazole derivative was obtained under acidic condition from cyclization of carbothioamide group. Most reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. All compounds obtained in this study were investigated for α-glucosidase inhibitor activity. Compounds 6a, 8a, 4b, 5b, 6b and 7b were potent inhibitors with IC50 values ranging from 10.49 to 158.2µM. This has described a new class of α-glucosidase inhibitors. Molecular docking studies were done for all compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.

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

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 (1)H NMR, (13)C 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.

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, (1) H NMR, (13) C 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.

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

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 (1) H NMR and (13) C NMR spectra and they were screened for their lipase inhibition and antioxidant activities. Compounds 4a, 4b, 5a, and 5b showed very good scavenging activity.

Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents.

N-Acyl imidates (2), reacting with 5-amino pyrazole (3), 2-aminobenzimidazole (4), 3-amino-1,2,4-triazole (5), 3,5-diamino-1,2,4-triazole (6), and 5-aminotetrazole (7) give pyrazolo[1,5-a][1,3,5]triazine (8), benzo[4,5]imidazo[1,2-a][1,3,5]triazine (9), [1,2,4]triazolo [2,3-a][1,3,5]triazine (10), [1,2,4]tri azolo[2,3-a][1,3,5]triazin-5-ylamine (12), and tetrazolo-[1,5-a][1,3,5]triazine (14) derivatives, respectively. The synthesized compounds were characterized on the basis of IR, (1)H-NMR, (13)C-NMR, and mass spectral data and elemental analyses results. Five of the newly synthesized compounds, 8a, 9a, 10a, 12a, and 14a, were selected by National Cancer Institute and screened for their anticancer activity against three cancer cell lines MCF7, NCI-H460, and SF-268, where 12a exhibited moderate anti-proliferation potential. 12a was, thus, further tested for anticancer activity against 60 human cancer cell lines and showed moderate growth inhibition potency. 12a showed a high growth inhibitory activity against A498 renal cancer cell line. All of the newly synthesized compounds 8-10, 12 and 14 were tested for their antioxidant capacity where they exhibited very high activity, even higher than the widely used reference antioxidants butylated hydroxytoluene and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Compound 12a also showed the highest antioxidant activity.

Three 1,2,4-triazole derivatives containing substituted benzyl and benzylamino groups.

The title compounds, 4-benzylamino-3-(4-methylbenzyl)-1H-1,2,4-triazol-5(4H)-one, C17H18N4O, (I), 3-(4-methylbenzyl)-4-(4-methylbenzylamino)-1H-1,2,4-triazol-5(4H)-one, C18H20N4O, (II), and 3-(4-chlorobenzyl)-4-(4-methylbenzylamino)-1H-1,2,4-triazol-5(4H)-one, C17H17ClN4O, (III), were obtained from the corresponding Schiff base in the presence of diglyme and NaBH(4). Each compound contains a 1,2,4-triazole ring and two benzene rings, which are essentially planar. The molecules are linked by a combination of intermolecular N-H...O and N-H...N hydrogen bonds. Additionally, there is a weak pi-pi stacking interaction in (I), involving the benzene ring of the aminobenzyl group and the partially aromatic 1,2,4-triazole moiety, with a centroid-centroid distance of 3.7397 (10) A.

Synthesis of 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones and their isatin-3-imine derivatives.

Iminoester hydrochlorides 1 have been synthesized. These compounds were then converted into ester ethoxycarbonyl hydrazones 2, from which in turn a new series of substituted 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones, 3, was then prepared. Finally a set of isatin imine derivatives 4 was obtained from the reaction of compounds 3 with isatin. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and (13)C-NMR spectra.

C-H...O and C-H...pi interactions in 1-acetyl-4-(p-chlorobenzylideneamino)-3-ethyl-4,5-dihydro-1H-1,2,4-triazol-5-one.

The title compound, C(13)H(13)ClN(4)O(2), contains both a phenyl and a triazole ring, both of which are approximately coplanar with the entire molecule. The triazole ring has substituents at the 1-, 2- and 4-positions. Intramolecular C-H.O and C-H.N interactions, together with intermolecular C-H.O and C-H.pi interactions, help to stabilize the structure.