Visible-Light-Mediated Amide Synthesis in Deep Eutectic Solvents

In the present study, for the first time environmentally friendly deep eutectic solvents (DESs) are used as reaction media to perform an efficient, simple and straightforward photocatalytic amide synthesis at room temperature using thioacids and amines. This method features mild conditions, a broad substrate scope, high yields (≤99%) under ambient conditions with air and moisture tolerance. Moreover, the applied operationally mild reaction conditions tolerate the presence of several different functional group substituents on the amine counterpart. Finally, the developed approach allows the recycling of the reaction medium and catalyst for at least three consecutive cycles without a significant decrease in the reaction yield.This research has been made possible thanks to the financial support received from the University of Alicante (VIGROB-316FI), the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00) and the Valencian Department of Innovation, Universities, Science and Digital Society (APOSTD/2020/235 and AICO/2021/013). The authors thank the Department of Pharmacy, Health and Nutritional Sciences (Department of Excellence funded according to the Law 232/2016) of the University of Calabria (Italy)

Eco-Friendly Synthesis of Lipophilic EGCG Derivatives and Antitumor and Antioxidant Evaluation

Epigallocatechin gallate (EGCG) was structurally modified to obtain EGCG fatty acid esters using an eco-friendly method employing Er(OTf)3 in 2-MeTHF as the catalyst. The products were purified in short times on a large scale using VERSAFLASH HTFP station on octadecyl-functionalized silica gel. The same Lewis acid showed to be a good catalyst for the synthesis of EGCG peracetated. The EGCG derivatives were assayed for their antioxidant capacity by DPPH assay and by ROS formation using the SH-SY5Y cell line

Green synthesis of privileged benzimidazole scaffolds using active deep eutectic solvent

The exploitation and use of alternative synthetic methods, in the face of classical procedures that do not conform to the ethics of green chemistry, represent an ever-present problem in the pharmaceutical industry. The procedures for the synthesis of benzimidazoles have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the development of compounds with pharmacological activity. Various benzimidazole derivatives exhibit important activities such as antimicrobial, antiviral, anti-inflammatory, and analgesic activities, and some of the already synthesized compounds have found very strong applications in medicine praxis. Here we report a selective and sustainable method for the synthesis of 1,2-disubstituted or 2-substituted benzimidazoles, starting from o-phenylenediamine in the presence of different aldehydes. The use of deep eutectic solvent (DES), both as reaction medium and reagent without any external solvent, provides advantages in terms of yields as well as in the work up procedure of the reaction.Fil: Gioia, Maria Luisa Di. Università della Calabria; ItaliaFil: Cassano, Roberta. Università della Calabria; ItaliaFil: Costanzo, Paola. Magna Græcia University. Department of Health Sciences; ItaliaFil: Herrera Cano, Natividad Carolina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Maiuolo, Loredana. Università della Calabria; ItaliaFil: Nardi, Monica. Magna Græcia University. Department of Health Sciences; ItaliaFil: Nicoletta, Fiore Pasquale. Università della Calabria; ItaliaFil: Oliverio, Manuela. Magna Græcia University. Department of Health Sciences; ItaliaFil: Procopio, Antonio. Magna Græcia University. Department of Health Sciences; Itali

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Biorenewable Deep Eutectic Solvent for Selective and Scalable Conversion of Furfural into Cyclopentenone Derivatives

The development of novel synthetic routes to produce bioactive compounds starting from renewable sources has become an important research area in organic and medicinal chemistry. Here, we present a low-cost procedure for the tunable and selective conversion of biomass-produced furfural to cyclopentenone derivatives using a mixture of choline chloride and urea as a biorenewable deep eutectic solvent (DES). The proposed medium is a nontoxic, biodegradable, and could be reused up to four times without any unfavorable effect on the reaction yield. The process is tunable, clean, cheap, simple and scalable and meets most of the criteria; therefore, it can be considered as an environmental sustainable process in a natural reaction medium

An Overview of the Latest Advances in the Catalytic Synthesis of Glycerol Carbonate

In recent years, the development of renewable energy alternatives to traditional fossil fuels has become one of the major challenges all over the world, due to the decline of fossil fuel reserves and their effect on global warming. Biodiesel has become a popular alternative energy source to reduce gas emissions compared to traditional fossil fuels. According to statistics, a nine-fold increase in global biofuel production between 2000 and 2020 was observed. However, its production generates a large amount of glycerol as a by-product, posing an environmental problem when disposed directly in landfills or by incineration. Therefore, low-value glycerol should be converted into high value-added derivatives. As glycerol carbonate is one of the most important derivatives of glycerol, this review aims to discuss the studies over the last ten years about glycerol carbonate synthetic methods, including the typical routes such as phosgene, esterification reaction, urea, oxidative and direct carbonylation as well as several rare synthetic procedures. At the same time, it summarizes the different catalytic reaction systems of each route comparing the advantages and disadvantages of various catalysts and evaluating their catalytic activity. Finally, the future development of glycerol carbonate synthesis is prospected from the point of view of development, technology research and industrialization

Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia

Ethnopharmacological relevance Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell. Aim of the study Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210BCR/ABLoncoprotein kinase. This chimeric protein is the target of a kinase inhibitor, imatinib, but the development of mutations in the ABL kinase domain resulting in drug resistance and several approaches to overcoming resistance have been study. In this concern, we investigated the effect of CCL extract on human K562 CML and K562 imatinib resistant (IMAR) cell proliferation and on p210BCR/ABLexpression. Materials and methods Chemical characterization of the CCL extracts was performed by GC/MS analysis and semipreparative RP-HPLC chromatography. Structural characterization of compounds was assessed by1Hâ13C NMR and LC/MS analysis. The effects of CCL extracts on the proliferation of K562 CML human cell line and K562 IMAR were screened by MTT assay. The p210BCR/ABLmRNA and protein expressions were analyzed by qRT-PCR and Western blot techniques respectively. Results We demonstrate that CCL extract affect cell viability of both K562 CML human cell line and K562 IMAR. The biocomponents of CCL were chemical characterized and we identify cynaropicrin and its deacyl derivative having the capability to down-regulate the p210BCR/ABLoncoprotein. Conclusions Our study suggests that the use of those molecules could represent a novel and promising strategy to potentiate the ability of imatinib or of its analogues to induce cancer growth arrest in CML and to delay or overcome the resistance of CML to chemotherapy