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Background: Benzothiazole is an organosulfur heterocyclic compound that has a considerable place in drug discovery due to significant pharmacological actions., Objective: The main objective of the present study was to synthesize some novel 2-(5-substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant activity using in silico and in vivo methods., Methods: A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by suitable spectral techniques. The synthesized compounds were evaluated for anticonvulsant activity using in silico and in vivo methods. In silico molecular docking study was performed using Molegro Virtual Docker software to analyze binding modes of compounds with the internal ligand of PDB ID: 1OHY and 1OHV; and in vivo pharmacological activities were tested for both generalized tonic-clonic seizures and generalized absence (petit mal) seizures using Maximal Electrical Shock and PTZ-induced seizure models, respectively., Results: Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3- benzothiazole (5a-5p) were successfully synthesized by finally refluxing 1, 3-benzothiazole-2-carboxyhydrazide with different aromatic acids in phosphoryl chloride. Docking results showed that compounds 5c, 5j, and 5m were found to have the highest number of H-bond interactions; i.e. 4, 4, and 7 respectively with target proteins 1OHY and 6, 3, and 4 respectively with target protein 1OHV, whereas phenytoin showed only two H-bonding with both proteins. In the Maximal electroshock seizure method, the synthesized compounds 5h, 5k and 5o demonstrated potent anticonvulsant activity against the tonic seizure with a significant decrease in tonic hind leg extension period with a mean duration of 7.9, 7.4, and 7.0 sec respectively, as compared to the other synthesized compounds. In contrast, in the PTZ-induced seizure model, compounds 5c, 5h, and 5m showed protection against clonic convulsion with significant elevation in the onset time of clonic convulsion at 311.2, 308.0, and 333.11 sec, respectively., Conclusion: Thus, from the results, it can be concluded that compound 5h, a benzothiazole derivative endowed with an oxadiazole ring, can be developed as a potential anticonvulsant agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ± 1.79 mg/dL, 154.39 ± 1.71 mg/dL, 167.36 ± 2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ± 1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ± 0.01 µM, 9.03 ± 0.12 µM and 11.96 ± 0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ± 0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ± 4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ± 1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski's rule of five., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a-l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a-e)] have been synthesized successfully from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI(50) values ranging from 0.49 to 48.0 μM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI(50) 0.49, TGI 19.9,LC(50) >100 and Log(10)GI(50) -6.30, Log(10)TGI -4.70, Log(10)LC(50) >-4.00)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1-(1H-benzo[d]imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2-yl)propan-1-ones (1b-A(7)(-)(26)) were synthesized under microwave irradiation in good yields. Further, compound 1b-A(7) was reacted with different secondary amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1b-A(7a)(-)(e)). The title compounds were screened for their in vitro anticancer activity at National Cancer Institute (NCI), USA; at a single dose (10 μM) in NCI 60 cell line panel and results showed significant to good anticancer activity. One compound, 1b-A(18) (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)propan-1-one, emerged as lead compound; it was selected for five-dose level screening and found to have significant growth inhibition activity., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A series of 2-(substituted-phenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazoles (3-15) were synthesized. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. The percentage inhibition in edema at different time intervals indicated that compounds 8, 11, 12, 14 and 15 exhibited good anti-inflammatory potential. The results illustrate that 2-(2-acetoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (15) and 2-(3,4-dimethoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (12) showed best anti-inflammatory activity among the series tested. Furthermore, activity is higher in case of chloro substitution as compared to methyl substitution. The compounds synthesized were also evaluated for their ulcerogenic and lipid peroxidation action and showed superior GI safety profile along with reduction in lipid peroxidation as compared to that of ibuprofen.

The synthesis of a series of 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones derived from 4-oxo-4-(biphenyl-4-yl)butanoic acid (fenbufen) is described. The structures of these compounds were supported by IR, (1)H NMR, mass spectrometric data and elemental analysis. These compounds were tested for their antiinflammatory, analgesic, ulcerogenic and lipid peroxidation actions. A few compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a fair number of compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action with reduced malondialdehyde (MDA) content, which is one of the byproducts of lipid peroxidation. In vitro COX-1 and COX-2 isozyme inhibition studies were also performed on some of the selected compounds. Compound 4i and 4h were found to be more selective towards COX-2 as indicated by COX-2 selectivity index of 36.06 and 29.05 (COX-2 IC(50)=1.5 microM and 1.8 microM) respectively.

Synthesis and biological evaluation of various aroylpropionic acid derivatives containing 1,3,4-Oxadiazole nucleus is reported here. The compounds (3a-w) were synthesized by cyclization of 3-aroylpropionic acids into 1,3,4-oxadiazole nucleus by treating with various aryl acid hydrazides in the presence of POCl(3). The structures of new compounds are supported by IR, (1)H NMR and MS data. These compounds were tested in vivo for their anti-inflammatory activity. All the compounds tested showed anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Seven (3c, g, i, j, m, o, p) out of 23 new compounds showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test with very less ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA), which is one of the byproducts of lipid peroxidation. Compound 3i and o showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid induced writhings and 0.7 and 0.65 of severity index respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen. The study showed that the cyclization of carboxylic group of aroylpropionic acids into an oxadiazole nucleus resulted in compounds having good anti-inflammatory and analgesic effects with reduced gastric irritation.

A novel series of 2-[3-(4-bromophenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazoles (4a-n) have been synthesized from 3-(4-bromobenzoyl)propionic acid (3) with the aim to get better anti-inflammatory and analgesic agents with minimum or without side effects (ulcerogenicity). Compound 3 was reacted with several aryl acid hydrazides (2a-n) in phosphorous oxychloride to obtain the title compounds. Structures of the synthesized compounds were supported by means of IR, 1H NMR and mass spectroscopy. Title compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and antibacterial activities. Antibacterial activity was expressed as the corresponding minimum inhibitory concentration (MIC). A fair number of compounds were found to have significant anti-inflammatory and analgesic activities, while a few compounds showed appreciable antibacterial activity. The newly synthesized compounds showed very low ulcerogenic action. The findings of the present study indicate that cyclization of the carboxylic group of 3 into novel 1,3,4-oxadiazole nucleus resulted in increased anti-inflammatory and analgesic activities with a significant decrease of ulcerogenic activity.

In the present investigation, two novel series of 2-[3-(4-chlorophenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole and 2-[3-(4-ethylphenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole were synthesized and tested for their antiinflammatory, analgesic, ulcerogenic and antibacterial actions. A fair number of compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a few compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action and moderate antibacterial action.

A receptor peroxisome proliferator activated receptor-gamma was targeted by series of new fatty acid chemical entities (M1-M22) which was designed, synthesized and characterized by spectral analysis. Metabolites molecular properties were calculated using Lipinski's rule of five using molinspiration online software. Docking studies were done on co-crystallized protein structure of PPAR γ, PDB-1FM9 showing M15, M17 and M8 to be best located in the active sites with scores -10.43, -10.21 and -10.00 respectively. The free binding energy estimation was done using model of Maestro 9.0 (Schrodinger) and lies between -80.15 to -61.26 kcal/mol which is significant as compared to that of standard (-48.58 Kcal/mol). Nine best docked derivatives were evaluated in-vivo for oral glucose tolerance and antihyperglycemic activity by streptozotocin induced diabetes model and M15 exhibited most promising antidiabetic activity more than the standard glibenclamide. The promising results encourage future investigation on fatty acids for development of active compounds. [ABSTRACT FROM AUTHOR]

We report herein one-pot synthesis and the antibacterial and antitubercular activities of 2,5-disubstituted-1,3,4-oxadiazole compounds obtained by hybridization of a well-known antitubercular agent isoniazid ( INH) with four broad-spectrum antibiotics belonging to fluoroquinolone ( FQ) class. The work is aimed at designing and developing potential antimicrobial agents having synergistic action due to the coupling of INH and FQ through the biologically active 1,3,4-oxadiazole nucleus. The synthesized compounds are expected to have low toxicity as compared to INH due to the absence of free hydrazide group in the chemical structure of the prepared derivatives. The antibacterial activities of the 1,3,4 oxadiazole derivatives were also tested against several Gram-positive and Gram-negative pathogenic bacterial strains. The antitubercular activity was evaluated against M. tuberculosis H37Rv strain, and the results were compared with that of the positive control INH. The title compounds showed excellent antimicrobial and promising antitubercular activity in comparison to the parent fluoroquinolones and INH, respectively. [ABSTRACT FROM AUTHOR]

The title compound, 1-(1H-benzimidazol-2-yl)-3-[5-(trichloromethyl)-1,3,4-oxadiazol-2-yl]propan-1-one (2) was synthesized successfully from 4-(1H-benzimidazol-2-yl)-4-oxobutanehydrazide (1) under microwave irradiation in good yield by reacting with trichloroacetic acid, and the structure of title compound was confirmed on the basis of IR, 1H-NMR, 13C-NMR, MS and CHN analyses results. [ABSTRACT FROM AUTHOR]