Synthesis of quinone-based heterocycles of broad-spectrum anticancer activity

A synthesis of benzo[e][1,2,4]triazines and 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones has been developed from reactions of amidrazones with 2-chloro-1,4-benzoquinone in EtOAc containing 0.5 mL of piperidine. This highly regioselective and one-pot process provided rapid access to 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones (60%-70%) and benzo[e][1,2,4]triazines (11%-18%). On reacting amidrazones with 5-hydroxy-1,4-naphthoquinone in an EtOAc/piperidine mixture, the reaction proceeded to give 5-hydroxy-2-(piperidin-1-yl)naphthalene-1,4-dione. The structures of the isolated products were proved by infrared, NMR (2D-NMR), mass spectra, and elemental analyses in addition to X-ray structure analysis. The reaction mechanisms are discussed. The anticancer screening of selected compounds showed broad-spectrum anticancer activity against most melanoma cancer cell lines, ovarian cancer OVCAR-3, central nervous system cancer SF-295 and U251, non-small cell lung cancer NCI-H23, renal cancer SN12C, and colon cancer HCT-15 and HCT-116. The selected compounds exhibited moderate to weak anticancer activity to other cell lines.Peer reviewe

Regioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the presence of diethyl azodicarboxylate and catalyzed by triethylamine

A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of amidrazones with ethyl azodicarboxylate and triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot process provides rapid access to highly diverse triazoles. The reaction was explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which would then react with amidrazones to give the substituted 3-methyltriazoles. A [2 + 3] cycloaddition reaction between two oxidized forms of amidrazones produced the second type of triazoles. X-ray structure analyses proved the structure of each type of product. [GRAPHICS] .Peer reviewe

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 years; 78.2% included were male with a median age of 37 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

Zinc Oxide Nanoparticles and Fe-Modified Activated Carbon Affecting the In Vitro Growth of Date Palm Plantlets cv. Medjool

The survival and growth of in vitro plantlets are still problematic for the date palm; thus, the application of nanotechnology may provide date palm plantlets that develop faster with enhanced growth and biochemical parameters. Moreover, the usage of Fe-modified activated carbon (Fe-AC) prepared from date palm pits instead of activated charcoal (AC) in tissue culture media during the current investigation can be considered an innovative approach. Furthermore, the effect of zinc oxide nanoparticles (ZnO-NPs) and bulk particles (ZnO-BPs) on the rooting and growth of date palm plantlets and on some physiological indices was also investigated. X-ray diffraction, dynamic light scattering, scanning electron microscopy, and transmission electron microscopy were used to characterize Fe-AC and ZnO-NPs. As detected from the characterization, the particle size was 720 nm for Fe-AC and 60 nm for ZnO-NPs. The obtained results indicated that AC significantly enhanced plantlet growth, plantlet height, number of leaves/plantlet, root length, number of roots/plantlet, and the concentrations of IAA, chlorophyll a and chlorophyll b compared with Fe-AC. On the other hand, sugars and phenols concentrations, and POD and PAL activities were highly increased with Fe-AC. There was no significant difference in terms of plant fresh weight (FW), leaf length, leaf width, protein, amino acids, and carotenoids. ZnO nanoparticles significantly improved plant height, leaf length, leaf width, root length, and the concentrations of IAA, chlorophylls a and b, and carotenoids; in contrast, the bulk form increased roots/plantlet, amino acids, and total sugars. Supplying the MS medium with combinations of ZnO-NPs or ZnO-BPs and AC or Fe-AC significantly increased all growth and physiological parameters. Plant height, leaf length, leaf width, root length, and the concentrations of IAA, protein, and chlorophylls a and b significantly increased when ZnO-NPs were combined with AC. Amino acids, total sugars, carotenoids, and phenols concentrations and the activities of POD and PAL increased when ZnO-BPs and Fe-AC were added together

Morpho-Anatomical and Biochemical Characterization of Embryogenic and Degenerative Embryogenic Calli of Phoenix dactylifera L.

The study of morpho-anatomical aspects, metabolic changes of proteins, antioxidant substances, as well as phenolic compounds in embryogenic callus (EC) and degenerative embryogenic callus (DEC) was the aim of the present investigation. Ability to form somatic embryos (SEs) was associated with the softness of the EC, which exhibited a white or creamy color and was composed of isodiametric cells containing dense cytoplasm, conspicuous nuclei and minimal vacuoles with observed mitotic activity. Furthermore, protein, reduced glutathione (GSH) and ascorbic acid (ASC) concentrations and the ratio between ASC and dehydroascorborbic acid (DHA) were increased significantly in the EC in comparison to the DEC. In addition, the phenolic extract of the EC was proved to have higher scavenging activity than the extract from the DEC. A loss of embryogenic competence in the DEC was correlated with the presence of more rigid clumps and such calli had a yellowish to brown color and no cell division could be observed in the cells of such aggregates as the cells had large vacuoles and they have very thick walls. Moreover, these morphological and anatomical observations of the DEC were accompanied by accumulations of the oxidized form of ascorbic acid (DHA), H2O2, total soluble phenolic compounds and overaccumulation of naringenin. Alternations in cellular metabolism can affect and regulate the morphogenesis of somatic embryos

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)