Spectral, thermal, antimicrobial studies for silver(I) complexes of pyrazolone derivatives

Background: Synthesize new complexes of Ag(I) to enhance efficacy or stability and also, pharmacological activities on the operation of pyrazolone's biological properties. Results: Efficient and high yielding pathways starting from the versatile and readily available 3-methyl-1-phenyl-5-pyrazolone by Knoevenagel condensation of a sequence of 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivatives (2a-c) have been formed by the reaction of various substituted aromatic aldehydes Used as ligands to synthesize Ag(I) chelates. Synthesized compounds and their complexes have been characterized by elemental analysis, magnetic and spectroscopic methods (IR, 13C, 1HNMR, mass) and thermal analysis. The spectrophotometric determinations suggest distorted octaedral geometry for all complexes. Both ligands and their metal complexes have also been tested for their antibacterial and antifungal efficacy. Conclusions: Newly synthesized compounds have shown potent antimicrobial activity. The results showed that the complex 's high activity was higher than its free ligands, and that Ag(I)-L3 had the highest activity.This research is not funded though any source to This publication was supported by Qatar University, internal grant number QUCG-CAM-20/21-2. The findings achieved herein are solely the responsibility of the authors

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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

Synthesis and biological activities of some fused pyran derivatives

Ethyl benzoylacetate (1) reacted with 2-benzylidenemalanonitrile to afford the corresponding pyrane derivative (2). The latter compound reacted with 2-benzylidenemalanonitrile, carbon disulfide, formamide and benzylidene cyclohexanone, respectively, to afford the corresponding pyrano derivatives (3–6). Compound 2 reacted with ethyl chloroacetate to give compound (8) which cyclized to compound (9) in the presence of sodium ethoxide. Treatment of compound (2) with acetic acid in the presence of sulfuric acid afforded compound (7) which converted to compound (10) when reacted with ethylchloroacetate. Compound (10) reacted with sodium ethoxide to give compound (11). The structure of the newly synthesized compounds has been established on the basis of their analytical and spectral data

Heterocyclization of polarized system: synthesis, antioxidant and anti-inflammatory 4-(pyridin-3-yl)-6-(thiophen-2-yl) pyrimidine-2-thiol derivatives

Abstract Background Chalcones are intent in the daily diet as a favorable chemotherapeutic compound; on the other hand thiophene moiety is present in a large number of bioactive molecules having diverse biological efficiency. Results Our current goal is the synthesis of (E)-1-(pyridin-3-yl)-3-(thiophen-2-yl) prop-2-en-1-one 3 that’s used as a starting compound to synthesize the novel pyrimidine-2-thiol, pyrazole, pyran derivatives. Chalcones 3 was prepared by condensation of 3-acetylpyridine with thiophene 2-carboxaldehyde which reacted with thiourea to obtain pyrimidinthiol derivative 4. Compound 4 was allowed to react with hydrazine hydrate to afford 2-hydrazinylpyrimidine derivative 5. Compound 5 was used as a key intermediate for a facile synthesis of the targets 6 and 7. In contrast, pyranone 8 was obtained by transformation of compound 5. Using as a precursor for the synthesis of new pyrazolo pyrimidine derivatives 9–10. The major incentive behind the preparation of these compounds was the immense biological activities associated to these heterocyclic derivatives. Conclusions The newly synthesized compounds (1–4) showed potent anti-inflammatory activities both in vitro and in vivo. They also exhibited promising antioxidant vitalities against α, α-diphenyl-β-picrylhydrazyl scavenging activity and lipid peroxidation. In conclusion, compound 1 showed a hopefully anti-inflammatory and antioxidant activities

Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future

Design, synthesis, biological evaluation, and bio-computational modeling of imidazo, thieno, pyrimidopyrimidine, pyrimidodiazepene, and motifs as antimicrobial agents

In the drug chemistry industry, synthesizing a talented exclusive series of aza-polyheterocyclic compounds was crucial. Aminopyrimidine nucleus reacted with two equivalents of benzaldehyde in the presence of KOH as a starting material to bring about imidazopyrimidine derivative, which experienced intermolecular cyclization using carbon disulfide, Br2/AcOH, and/or HNO2 to produce thiazole, thieno, and/or nitro pyrimidine derivative, respectively. Accordingly, the nucleus of Aminopyrimidine was prepared and used to develop the novel polyheterocyclic systems acylated with two moles of succinic anhydride to furnish the imidazolopyrimidine derivative. Benzylidene ethyl cyanoacetate and aminopyrimidine undergo (3 + 4) intermolecular cycloaddition 1,3 H shift followed by hydrolysis and after CO2 evolution provided diazepine derivative. The diazepine derivative was attained due to the cyclo-condensation of the starting material and acetylacetone. Moreover, the structure of the novel synthesized compound series was exploited and verified via spectroscopic approaches. The synthesized series were tested for antimicrobial activity against gram-positive and gram-negative bacterial strains and antifungal activity. The thienopyrimidine derivatives and diazepine exhibited unusual antimicrobial activity. Furthermore, the molecular docking studies confirmed the biological studies with Molecular Operating Environment and petro orisis molinspiration studies, which proved the activity of compounds 4, 5, 7, 10, 13, and 16