Synthesis and biological evaluation of some heterocyclic compounds

Cancer is one of the most striking diseases that has a potential impact on human health with high mortality rate. During the last century many anticancer agents have emerged but unfortunately, these agents could not provide effective solutions for cancer treatment due to side effects and resistance. All over the world, asking for new anticancer agents is still a major goal for medicinal chemists. Pyrrole and pyrrolo[2,3-d]pyrimidine scaffolds are very interesting bioactive core exhibiting several biological activities as anticancer, anti-inflammatory, antimicrobial activities. Herein, we highlighted on the anticancer activity of the pyrrole and pyrrolo[2,3-d]pyrimidine derivatives which are reported to possess anticancer activity and many of them are in market or still in clinical trials. This work deals with design and synthesis of new pyrrole and pyrrolopyrimidine derivatives. The new compounds were screened for their cytotoxic activity against HepG2 and MCF7in vitro. The most active compounds were evaluated for their VEGFR-2 inhibition in vitr

Simultaneous determination of sulpiride and mebeverine by HPLC method using fluorescence detection: application to real human plasma

A new simple, rapid and sensitive reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of sulpiride (SUL) and mebeverine Hydrochloride (MEB) in the presence of their impurities and degradation products. The separation of these compounds was achieved within 6 min on a 250 mm, 4.6 mm i.d., 5 m particle size Waters®-C18 column using isocractic mobile phase containing a mixture of acetonitrile and 0.01 M dihydrogenphosphate buffer (45:55) at pH = 4.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence-detection at excitation 300 nm and emission at 365 nm. The concentration-response relationship was linear over a concentration range of 10- 100 ng/mL for both MEB and SUL with a limit of detection 0.73 ng/mL and 0.85 ng/mL for MEB and SUL respectively. The proposed method was successfully applied for the analysis of both MEB and SUL in bulk with average recoveries of 100.22 ± 0.757% and 99.96 ± 0.625% respectively, and in commercial tablets with average recoveries of 100.04 ± 0.93% and 100.03 ± 0.376% for MEB and SUL respectively. The proposed method was successfully applied to the determination of MEB metabolite (veratic acid) in real plasma simultaneously with SUL. The mean% recoveries (n = 3) for both MEB metabolite (veratic acid) and SUL were 100.36 ± 2.92 and 99.06 ± 2.11 for spiked human plasma respectively. For real human plasma, the mean% recoveries (n = 3) were and respectively

Suction circuit flushing with chlorhexidine decreases ventilator-associated pneumonia: a quasi-experimental study

BackgroundEndotracheal suctioning of mechanically ventilated patients differs across the world. In many low and middle-income countries, endotracheal suctioning is often performed with a sterile suctioning catheter that is used for 12 h or during the length of one nursing shift. The effect of flushing multiple used endotracheal suction system with chlorhexidine after suctioning to reduce ventilator associated pneumonia (VAP) remains unclear.AimThe aim of the study is to assess the effectiveness of flushing multiple-used open endotracheal suction catheters and suctioning system with chlorhexidine gluconate 0.2% to reduce VAP in mechanically ventilated patients in a resource-limited Intensive Care Unit (ICU).MethodsDue to the difficulty of blinding the intervention for nurses who perform endo-tracheal suction procedures, we adopted a quasi-experimental method with a randomized controlled trial design. A sample of 136 ICU patients were allocated to the intervention (n = 68) or control group (n = 68) between May and November 2020. The intervention was flushing the multiple-used suction catheter and suction system with 40ml chlorhexidine gluconate 0.2% and in the control group we used normal saline to flush the catheter and suction system. The primary outcome was incidence of VAP and the cost of the flushing solutions was the secondary outcome measure.ResultsPatients in the intervention group had a lower incidence of VAP compared to patients in the control group; 15 (22.1%) vs 29 (42.6%), p = 0.01. The incidence of late-onset VAP was 26.2% in the intervention group and 49% in the control group (p = 0.026) and the early-onset VAP was 13.2% in the intervention group and 25% in the control group (p = 0.081). Chlorhexidine gluconate 0.2% reduced the cost of suction system flushing (median: 78.4 vs 300 EGP, p < 0.001).ConclusionUsing chlorhexidine gluconate 0.2% to flush multiple-used suctioning catheters after every endo-tracheal suction procedure might reduce the incidence of VAP in mechanically ventilated patients. Chlorhexidine gluconate 0.2% can be a cost-effective solution for flushing the suction circuit. Nurses working in resource-limited ICUs and using suctioning catheters multiple times might consider using chlorhexidine gluconate 0.2% instead of normal saline or distilled water when flushing the suction system.Clinical trial registrationClinicalTrials.gov, identifier NCT05206721

Synthesis and evaluation of anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities of some 3H-quinazolin-4-one derivatives

Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA2, and AmPLA2. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs

Crystal structure of (E)-2-(4-hydroxy-3-methoxybenzylidene)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one, C19H18O4

C19H18O4, orthorhombic, Pbcn, a=21.1472(8) Å, b= 9.7978(4) Å, c=14.5181(6) Å, V =3008.1(2) Å3, Z =8, Rgt(F)=0.0520, wRref(F2)=0.1194, T =100(2)

Molecular Epidemiology and Evolutionary Analysis of Avian Influenza A(H5) Viruses Circulating in Egypt, 2019–2021

The highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in Egypt in late 2016. Since then, the virus has spread rapidly among different poultry sectors, becoming the dominant HPAI H5 subtype reported in Egypt. Different genotypes of the HPAI H5N8 virus were reported in Egypt; however, the geographic patterns and molecular evolution of the Egyptian HPAI H5N8 viruses are still unclear. Here, extensive epidemiological surveillance was conducted, including more than half a million samples collected from different poultry sectors (farms/backyards/live bird markets) from all governorates in Egypt during 2019–2021. In addition, genetic characterization and evolutionary analyses were performed using 47 selected positive H5N8 isolates obtained during the same period. The result of the conducted surveillance showed that HPAI H5N8 viruses of clade 2.3.4.4b continue to circulate in different locations in Egypt, with an obvious seasonal pattern, and no further detection of the HPAI H5N1 virus of clade 2.2.1.2 was observed in the poultry population during 2019–2021. In addition, phylogenetic and Bayesian analyses revealed that two major genotypes (G5 and G6) of HPAI H5N8 viruses were continually expanding among the poultry sectors in Egypt. Notably, molecular dating analysis suggested that the Egyptian HPAI H5N8 virus is the potential ancestral viruses of the European H5N8 viruses of 2020–2021. In summary, the data of this study highlight the current epidemiology, diversity, and evolution of HPAI H5N8 viruses in Egypt and call for continuous monitoring of the genetic features of the avian influenza viruses in Egypt

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field