Reaction of 2,5-Disubstituted-1,3,4-oxadiazoles

Some 5-aryl-2-mercapto-1,3,4-oxadiazole (I) reacted with maleic anhydride, maleic acid and p-benzoquinone affording 2-(5-aryl- -1,3,4-oxadiazol-2-ylthio)succinic anhydrides (II), 2-(5-aryl-1,3,4- -oxadiazol-2-ylthio)succinic acids (III) and 2-(2,5 dihydroxyphenylthio)- 5-aryl-l,3,4-oxadiazoles (IV), respectively. Treatment of 2- methylthio-5-phenyl-l,3-oxadiazole (V) with amines gives 2-[(alkyl or aryl)-amino]-5-phenyl-l,3,4-oxadiazoles (VI). Compound VIe condensed with aromatic aldehydes to give 2-(4-cinnamoylanilino)- 5-phenyl-l,3,4-oxadiazoles (VII) which on bromination afforded the dibromo derivative VIlI and on treatment with hydroxylamine afforded 2-[4-(5-aryl-2-isoxazolin-3-yl)anilino]-5-phenyl-1,3,4-oxadiazoles (IX). Reacting VII with hydrazine hydrate gave 2-[4-(5-aryl-2-pyrazolin-3-yl)anilino]-5-phenyl-l,3,4-oxadiazoles (X), while on treatement VII with acetylacetone and ethylacetoacetate afforded 2- [4-(4-acetyl or carbethoxy-5-phenyl-l-cyclohexen -3-one- -1-yl)anilino]-5-phenyl-l,3,4-oxadiazoles (XIIa, b), respectively

Some Chemical Aspects of Tetrahydro-1-thiopyran-4-one Derivatives

3,5-Diarylmethylene-2,6-diphenyltetrahydrothiopyran-4-thiones, 2, reacted with two or four moles of bromine to form 3-aryimethylene 5-bromoarylmethylene- 2,6-dipheny1tetrahydrothiopyran- -4-thione, 3, and 3-arylmethylene-5-bromoarylmethylene-2,6-dibromo- 2,6-diphenyltetrahydrothiopyran-4-thione, 5, respectively. Compound 2a reacted with amines giving 2,6-diphenyl-5-iminophenylmethyl- 3-phenylmethylenetetrahydrothiopyran-4-thiones, 6. Diphenydiazomethane and 9-diazofluorene converted 2a into 4-diphenylethylene- 2,6-dipheny1-3,5 diphenylmethylenetetrahydrothiopyran, 7, and 2,6-diphenyl-3,5-diphenylmethylene-4-(9-fluorenylidene) tetrahydrothiopyran, 8, respectively. Compounds 2 with copper-bronze afforded 3,3\u27,5,5\u27-tetraarylmethylene-2,2\u27 ,6,6\u27-tetraphenyl-Lr-thio- 4,4\u27 dipyranylidenes

Non-invasive index of liver fibrosis induced by alcohol, thioacetamide and schistosomal infection in mice

<p>Abstract</p> <p>Background</p> <p>Non invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice.</p> <p>Methods</p> <p>Fibrosis was generated by thioacetamide (TAA), chronic intake of ethanol, or infection with <it>S. mansoni </it>in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel) were monitored. The following methods were employed: (i) The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii) Determination of hepatic hydroxyproline and collagen; and (iii) Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice.</p> <p>Results</p> <p>The index is composed of 4 serum variable including total proteins, γ-GT, bilirubin and reduced glutathione (GSH), measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2), starting with healthy liver (corresponding to stage 0) to advanced fibrosis (corresponding stage 3).Receiver operating characteristic curves (ROC) for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC) were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively). The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation.</p> <p>Conclusion</p> <p>The index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver-specific, easy to implement, reliable, and inexpensive. It proved to be accurate in discriminating precirrhotic stages.</p

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Examining the Concentration of Organonitrogen Pesticides in Water at Nile Delta, Egypt

In this study, Organonitrogen pesticides (ONPs) levels were determined in surface and groundwater samples from El-Rahawy area in the southwestern part of Nile Delta, Egypt. Gas Chromatography with Nitrogen Phosphorous Detector (GC-NPD) was proposed to determine the concentration of eleven ONPs, molinate, atrazine, simazine, prometon, propazine, prometryn, simetryn, ametryn, alachlor, terbutryn and metolachlor during winter and summer seasons. The most abundant components were molinate and propazine. The total concentrations of ONPs in the surface samples were from 3.9636 to 75.878 ng L-1 while in groundwater were below the detection limit i.e. 0.02 ng L-1. The results have been discussed and compared with Canadian water quality guidelines for irrigation and fresh water

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

<div><p></p><p>4-Arylidene-imidazole derivatives (<b>4a</b>,<b>b</b>) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (<b>1</b>) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (<b>2</b>). Reaction of <b>1</b> with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates <b>5a</b>-<b>c</b>. Reaction of <b>1</b> with 3-phenyl-1H-quinazoline-2,4-dione (<b>6a</b>) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (<b>6b</b>) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (<b>7</b>). Moreover, on treating <b>1</b> with 2-phenylbenzo[d][1,3]thiazine-4-thione (<b>8</b>), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (<b>9</b>) was obtained in 65% yield. Reaction of <b>1</b> with 4-sulfonylaminoacetic acid derivatives (<b>10a</b>,<b>b</b>) afforded the corresponding sulfonamides (<b>11a</b>,<b>b</b>), respectively. Acid hydrolysis of <b>11a</b> afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (<b>12</b>). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (<b>14</b>) was prepared by reacting compound <b>1</b> with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (<b>16</b>) was obtained by oxidation of <b>1</b> with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.</p> <p>[Supplementary materials are available for this article. Go to the publisher's online edition of <i>Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.</i>]</p> </div

Value of apparent diffusion coefficient and magnetic resonance spectroscopy in the identification of various pathological subtypes of parotid gland tumors

Background and purpose: Pre-operative imaging has a major role in surgical planning of parotid gland tumors. Aim: To assess the role of the combined techniques of ADC generated from DWI and MR spectroscopy in identification of various pathological subtypes of parotid gland tumors. Patients and methods: Prospective study was conducted on 25 patients with primary parotid tumors (11 males, 14 females, age ranged 22–79 years with mean of 53.4 ± 13.6 years). DWI and MRS were performed for all patients and the results were correlated with histopathological findings. Results: The 18 (72%) benign and 7 (28%) malignant tumors consisted of 11 pleomorphic adenomas, 7 Warthin tumors, and 7 malignant tumors. The mean ADC value for pleomorphic adenomas was 1.89 ± 0.18 × 10−3 mm2/s, for Warthin tumors was 0.92 ± 0.22 × 10−3 mm2/s, and for the malignant tumors was 1.03 ± 0.13 × 10−3 mm2/s, significant difference was seen between benign and malignant tumors (P = 0.037). The mean values of Cho/Cr ratios were 3.37 ± 0.78, 5.9 ± 1.75 and 1.72 ± 0.41, for pleomorphic adenomas, Warthin tumors, and malignant tumors, respectively. Difference was significant between benign and malignant tumors (P = 0.001). Conclusion: DWI and MRS are useful noninvasive diagnostic modalities in identification of various pathological subtypes of parotid tumors

Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors

Abstract A series of novel azepine derivatives based on quinazolinone moiety was synthesized through the reaction of quinazolinone chalcones (2a–d) either with 2-amino aniline in acidic medium to give diazepines (3a–d) or with 2-aminophenol to offer oxazepine (4a–d). The structure of the synthesized compounds was confirmed via melting points, elemental analyses, and different spectroscopic techniques. Moreover, these newly compounds mode of action was investigated in-silico using molecular docking against the outer membrane protein A (OMPA), exo-1,3-beta-glucanase for their antimicrobial activity, and against Smoothened (SMO), transcription factor glioma-associated homology (SUFU/GLI-1), the main proteins of Hedgehog signaling pathway to inspect their anticancer potential. Our results showed that, diazepine (3a) and oxazepine (4a) offered the highest binding energy against the target OMPA/ exo-1,3-beta-glucanase proteins and exhibited the potent antimicrobial activities against E. coli, P. aeruginosa, S. aureus, B. subtilis, C. Albicans and A. flavus. As well, diazepine (3a) and oxazepine (4a) achieved the best results among the other compounds, in their binding energy against the target SMO, SUFU/GLI-1 proteins. The in-vitro cytotoxic study was done for them on panel of cancer cell lines HCT-116, HepG2, and MCF-7 and normal cell line WI-38. Conclusively, it was revealed that molecular docking in-silico simulations and the in-vitro experiments were agreed. As a result, our findings elucidated that diazepine (3a) and oxazepine (4a), have the potential to be used as antimicrobial agents and as possible cancer treatment medications